The role of Bcl-2 family members in tumorigenesis

Biochimica et Biophysica Acta - Molecular Cell Research

Volumn 1644, Issue 2-3, 2004, Pages 229-249

  Kirkin, Vladimir ^a   Joos, Stefan ^b   Zörnig, Martin ^a  

^a INSTITUTE FOR TUMOR BIOLOGY AND EXPERIMENTAL THERAPY   (Germany)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

Author keywords

Bcl 2 family; Cell cycle; Chemoresistance; Clinical therapy; Radiation; Tumorigenesis

Indexed keywords

BH3 PROTEIN; CYTOCHROME C; ONCOPROTEIN; PROTEIN BAK; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN MCL 1;

APOPTOSIS; CARCINOGENESIS; CELL CYCLE; CELL DEATH; CONFORMATION; HUMAN; MALIGNANT NEOPLASTIC DISEASE; MITOCHONDRIAL MEMBRANE; MITOCHONDRION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SEQUENCE HOMOLOGY; SURVIVAL;

ANIMALS; APOPTOSIS; BCL-2 HOMOLOGOUS ANTAGONIST-KILLER PROTEIN; BCL-2-ASSOCIATED X PROTEIN; CELL CYCLE; DRUG RESISTANCE, NEOPLASM; HUMANS; MEMBRANE PROTEINS; MICE; MITOCHONDRIA; NEOPLASMS; ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-BCL-2;

EID: 1442286330     PISSN: 01674889     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbamcr.2003.08.009     Document Type: Review

References (245)

1. Strasser A., O'Connor L., Dixit V.M. Apoptosis signaling. Annu. Rev. Biochem. 69:2000;217.
2. Hanahan D., Weinberg R.A. The hallmarks of cancer. Cell. 100:2000;57.
3. Hueber A.O., Evan G.I. Traps to catch unwary oncogenes. Trends Genet. 14:1998;364.
4. Harris A.L. Hypoxia - a key regulatory factor in tumour growth. Nat. Rev., Cancer. 2:2002;38.
5. Grossmann J. Molecular mechanisms of "detachment-induced apoptosis-Anoikis" Apoptosis. 7:2002;247.
6. Liu Q.A., Hengartner M.O. The molecular mechanism of programmed cell death in C. elegans. Ann. N.Y. Acad. Sci. 887:1999;92.
7. Borner C. The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol. Immunol. 39:2003;615.
8. Petros A.M., Medek A., Nettesheim D.G., Kim D.H., Yoon H.S., Swift K., Matayoshi E.D., Oltersdorf T., Fesik S.W. Solution structure of the antiapoptotic protein bcl-2. Proc. Natl. Acad. Sci. U. S. A. 98:2001;3012.
9. Sattler M., Liang H., Nettesheim D., Meadows R.P., Harlan J.E., Eberstadt M., Yoon H.S., Shuker S.B., Chang B.S., Minn A.J., Thompson C.B., Fesik S.W. Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science. 275:1997;983.
10. Suzuki M., Youle R.J., Tjandra N. Structure of Bax: coregulation of dimer formation and intracellular localization. Cell. 103:2000;645.
11. Conus S., Kaufmann T., Fellay I., Otter I., Rosse T., Borner C. Bcl-2 is a monomeric protein: prevention of homodimerization by structural constraints. EMBO J. 19:2000;1534.
12. Cheng E.H., Kirsch D.G., Clem R.J., Ravi R., Kastan M.B., Bedi A., Ueno K., Hardwick J.M. Conversion of Bcl-2 to a Bax-like death effector by caspases. Science. 278:1997;1966.
13. Krajewski S., Krajewska M., Shabaik A., Miyashita T., Wang H.G., Reed J.C. Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2. Am. J. Pathol. 145:1994;1323.
14. Krajewski S., Krajewska M., Reed J.C. Immunohistochemical analysis of in vivo patterns of Bak expression, a proapoptotic member of the Bcl-2 protein family. Cancer Res. 56:1996;2849.
15. Hsu S.Y., Kaipia A., McGee E., Lomeli M., Hsueh A.J. Bok is a pro-apoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti-apoptotic Bcl-2 family members. Proc. Natl. Acad. Sci. U. S. A. 94:1997;12401.
16. Lindsten T., Ross A.J., King A., Zong W.X., Rathmell J.C., Shiels H.A., Ulrich E., Waymire K.G., Mahar P., Frauwirth K., Chen Y., Wei M., Eng V.M., Adelman D.M., Simon M.C., Ma A., Golden J.A., Evan G., Korsmeyer S.J., MacGregor G.R., Thompson C.B. The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol. Cell. 6:2000;1389.
17. Zong W.X., Lindsten T., Ross A.J., MacGregor G.R., Thompson C.B. BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Genes Dev. 15:2001;1481.
18. Hunter J.J., Parslow T.G. A peptide sequence from Bax that converts Bcl-2 into an activator of apoptosis. J. Biol. Chem. 271:1996;8521.
19. Nechushtan A., Smith C.L., Hsu Y.T., Youle R.J. Conformation of the Bax C-terminus regulates subcellular location and cell death. EMBO J. 18:1999;2330.
20. Griffiths G.J., Dubrez L., Morgan C.P., Jones N.A., Whitehouse J., Corfe B.M., Dive C., Hickman J.A. Cell damage-induced conformational changes of the pro-apoptotic protein Bak in vivo precede the onset of apoptosis. J. Cell Biol. 144:1999;903.
21. Schlesinger P.H., Gross A., Yin X.M., Yamamoto K., Saito M., Waksman G., Korsmeyer S.J. Comparison of the ion channel characteristics of proapoptotic BAX and antiapoptotic BCL-2. Proc. Natl. Acad. Sci. U. S. A. 94:1997;11357.
22. Tsujimoto Y., Shimizu S. VDAC regulation by the Bcl-2 family of proteins. Cell Death Differ. 7:2000;1174.
23. Zamzami N., Kroemer G. The mitochondrion in apoptosis: how Pandora's box opens. Nat. Rev., Mol. Cell Biol. 2:2001;67.
24. Antonsson B., Montessuit S., Lauper S., Eskes R., Martinou J.C. Bax oligomerization is required for channel-forming activity in liposomes and to trigger cytochrome c release from mitochondria. Biochem. J. 345:2000;271.
25. Hsu Y.T., Youle R.J. Bax in murine thymus is a soluble monomeric protein that displays differential detergent-induced conformations. J. Biol. Chem. 273:1998;10777.
26. Simonian P.L., Grillot D.A., Andrews D.W., Leber B., Nunez G. Bax homodimerization is not required for Bax to accelerate chemotherapy-induced cell death. J. Biol. Chem. 271:1996;32073.
27. Kuwana T., Mackey M.R., Perkins G., Ellisman M.H., Latterich M., Schneiter R., Green D.R., Newmeyer D.D. Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell. 111:2002;331.
28. Cory S., Adams J.M. The Bcl2 family: regulators of the cellular life-or-death switch. Nat. Rev., Cancer. 2:2002;647.
29. Grinberg M., Sarig R., Zaltsman Y., Frumkin D., Grammatikakis N., Reuveny E., Gross A. tBID homooligomerizes in the mitochondrial membrane to induce apoptosis. J. Biol. Chem. 277:2002;12237.
30. Wei M.C., Lindsten T., Mootha V.K., Weiler S., Gross A., Ashiya M., Thompson C.B., Korsmeyer S.J. tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev. 14:2000;2060.
31. Letai A., Bassik M.C., Walensky L.D., Sorcinelli M.D., Weiler S., Korsmeyer S.J. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cells. 2:2002;183.
32. Sugiyama T., Shimizu S., Matsuoka Y., Yoneda Y., Tsujimoto Y. Activation of mitochondrial voltage-dependent anion channel by a pro-apoptotic BH3-only protein Bim. Oncogene. 21:2002;4944.
33. Yamaguchi H., Wang H.G. Bcl-XL protects BimEL-induced Bax conformational change and cytochrome C release independent of interacting with Bax or BimEL. J. Biol. Chem. 277:2002;41604.
34. Huang D.C., Strasser A. BH3-only proteins - essential initiators of apoptotic cell death. Cell. 103:2000;839.
35. Bouillet P., Metcalf D., Huang D.C., Tarlinton D.M., Kay T.W., Kontgen F., Adams J.M., Strasser A. Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science. 286:1999;1735.
36. Puthalakath H., Villunger A., O'Reilly L.A., Beaumont J.G., Coultas L., Cheney R.E., Huang D.C., Strasser A. Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis. Science. 293:2001;1829.
37. Nakano K., Vousden K.H. PUMA, a novel proapoptotic gene, is induced by p53. Mol. Cell. 7:2001;683.
38. Oda E., Ohki R., Murasawa H., Nemoto J., Shibue T., Yamashita T., Tokino T., Taniguchi T., Tanaka N. Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science. 288:2000;1053.
39. Yu J., Zhang L., Hwang P.M., Kinzler K.W., Vogelstein B. PUMA induces the rapid apoptosis of colorectal cancer cells. Mol. Cell. 7:2001;673.
40. Zha J., Harada H., Yang E., Jockel J., Korsmeyer S.J. Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell. 87:1996;619.
41. Wang H.G., Pathan N., Ethell I.M., Krajewski S., Yamaguchi Y., Shibasaki F., McKeon F., Bobo T., Franke T.F., Reed J.C. Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD. Science. 284:1999;339.
42. Li H., Zhu H., Xu C.J., Yuan J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell. 94:1998;491.
43. Luo X., Budihardjo I., Zou H., Slaughter C., Wang X. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell. 94:1998;481.
44. Chou J.J., Li H., Salvesen G.S., Yuan J., Wagner G. Solution structure of BID, an intracellular amplifier of apoptotic signaling. Cell. 96:1999;615.
45. McDonnell J.M., Fushman D., Milliman C.L., Korsmeyer S.J., Cowburn D. Solution structure of the proapoptotic molecule BID: a structural basis for apoptotic agonists and antagonists. Cell. 96:1999;625.
46. Zha J., Weiler S., Oh K.J., Wei M.C., Korsmeyer S.J. Posttranslational N-myristoylation of BID as a molecular switch for targeting mitochondria and apoptosis. Science. 290:2000;1761.
47. Puthalakath H., Huang D.C., O'Reilly L.A., King S.M., Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol. Cell. 3:1999;287.
48. Zornig M., Hueber A., Baum W., Evan G. Apoptosis regulators and their role in tumorigenesis. Biochim. Biophys. Acta. 1551:2001;F1.
49. Muchmore S.W., Sattler M., Liang H., Meadows R.P., Harlan J.E., Yoon H.S., Nettesheim D., Chang B.S., Thompson C.B., Wong S.L., Ng S.L., Fesik S.W. X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature. 381:1996;335.
50. Strasser A., Huang D.C., Vaux D.L. The role of the bcl-2/ced-9 gene family in cancer and general implications of defects in cell death control for tumourigenesis and resistance to chemotherapy. Biochim. Biophys. Acta. 1333:1997;F151.
51. Sherr C.J. The INK4a/ARF network in tumour suppression. Nat. Rev., Mol. Cell Biol. 2:2001;731.
52. Miyashita T., Reed J.C. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell. 80:1995;293.
53. Bakhshi A., Jensen J.P., Goldman P., Wright J.J., McBride O.W., Epstein A.L., Korsmeyer S.J. Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell. 41:1985;899.
54. Cleary M.L., Smith S.D., Sklar J. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell. 47:1986;19.
55. Tsujimoto Y., Finger L.R., Yunis J., Nowell P.C., Croce C.M. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science. 226:1984;1097.
56. Hockenbery D., Nunez G., Milliman C., Schreiber R.D., Korsmeyer S.J. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 348:1990;334.
57. Vaux D.L., Cory S., Adams J.M. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature. 335:1988;440.
58. Merry D.E., Veis D.J., Hickey W.F., Korsmeyer S.J. bcl-2 protein expression is widespread in the developing nervous system and retained in the adult PNS. Development. 120:1994;301.
59. Hockenbery D.M., Zutter M., Hickey W., Nahm M., Korsmeyer S.J. BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc. Natl. Acad. Sci. U. S. A. 88:1991;6961.
60. Merino R., Ding L., Veis D.J., Korsmeyer S.J., Nunez G. Developmental regulation of the Bcl-2 protein and susceptibility to cell death in B lymphocytes. EMBO J. 13:1994;683.
61. Fulcher D.A., Basten A. Influences on the lifespan of B cell subpopulations defined by different phenotypes. Eur. J. Immunol. 27:1997;1188.
62. Nunez G., Hockenbery D., McDonnell T.J., Sorensen C.M., Korsmeyer S.J. Bcl-2 maintains B cell memory. Nature. 353:1991;71.
63. Strasser A., Whittingham S., Vaux D.L., Bath M.L., Adams J.M., Cory S., Harris A.W. Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. Proc. Natl. Acad. Sci. U. S. A. 88:1991;8661.
64. Linette G.P., Grusby M.J., Hedrick S.M., Hansen T.H., Glimcher L.H., Korsmeyer S.J. Bcl-2 is upregulated at the CD4+ CD8+ stage during positive selection and promotes thymocyte differentiation at several control points. Immunity. 1:1994;197.
65. Sentman C.L., Shutter J.R., Hockenbery D., Kanagawa O., Korsmeyer S.J. bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes. Cell. 67:1991;879.
66. Bouillet P., Purton J.F., Godfrey D.I., Zhang L.C., Coultas L., Puthalakath H., Pellegrini M., Cory S., Adams J.M., Strasser A. BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes. Nature. 415:2002;922.
67. Strasser A., Harris A.W., Cory S. bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell. 67:1991;889.
68. Strasser A., Harris A.W., von Boehmer H., Cory S. Positive and negative selection of T cells in T-cell receptor transgenic mice expressing a bcl-2 transgene. Proc. Natl. Acad. Sci. U. S. A. 91:1994;1376.
69. Rathmell J.C., Lindsten T., Zong W.X., Cinalli R.M., Thompson C.B. Deficiency in Bak and Bax perturbs thymic selection and lymphoid homeostasis. Nat. Immunol. 3:2002;932.
70. Newton K., Harris A.W., Bath M.L., Smith K.G., Strasser A. A dominant interfering mutant of FADD/MORT1 enhances deletion of autoreactive thymocytes and inhibits proliferation of mature T lymphocytes. EMBO J. 17:1998;706.
71. Matsuzaki Y., Nakayama K., Tomita T., Isoda M., Loh D.Y., Nakauchi H. Role of bcl-2 in the development of lymphoid cells from the hematopoietic stem cell. Blood. 89:1997;853.
72. Nakayama K., Negishi I., Kuida K., Sawa H., Loh D.Y. Targeted disruption of Bcl-2 alpha beta in mice: occurrence of gray hair, polycystic kidney disease, and lymphocytopenia. Proc. Natl. Acad. Sci. U. S. A. 91:1994;3700.
73. Veis D.J., Sorenson C.M., Shutter J.R., Korsmeyer S.J. Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell. 75:1993;229.
74. Kamada S., Shimono A., Shinto Y., Tsujimura T., Takahashi T., Noda T., Kitamura Y., Kondoh H., Tsujimoto Y. bcl-2 deficiency in mice leads to pleiotropic abnormalities: accelerated lymphoid cell death in thymus and spleen, polycystic kidney, hair hypopigmentation, and distorted small intestine. Cancer Res. 55:1995;354.
75. Sorenson C.M., Rogers S.A., Korsmeyer S.J., Hammerman M.R. Fulminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice. Am. J. Physiol. 268:1995;F73.
76. Nakayama K., Negishi I., Kuida K., Shinkai Y., Louie M.C., Fields L.E., Lucas P.J., Stewart V., Alt F.W.et al. Disappearance of the lymphoid system in Bcl-2 homozygous mutant chimeric mice. Science. 261:1993;1584.
77. Yamamura K., Kamada S., Ito S., Nakagawa K., Ichihashi M., Tsujimoto Y. Accelerated disappearance of melanocytes in bcl-2-deficient mice. Cancer Res. 56:1996;3546.
78. Boot-Handford R.P., Michaelidis T.M., Hillarby M.C., Zambelli A., Denton J., Hoyland J.A., Freemont A.J., Grant M.E., Wallis G.A. The bcl-2 knockout mouse exhibits marked changes in osteoblast phenotype and collagen deposition in bone as well as a mild growth plate phenotype. Int. J. Exp. Pathol. 79:1998;329.
79. Dominov J.A., Dunn J.J., Miller J.B. Bcl-2 expression identifies an early stage of myogenesis and promotes clonal expansion of muscle cells. J. Cell Biol. 142:1998;537.
80. Hu Y., Benedict M.A., Wu D., Inohara N., Nunez G. Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation. Proc. Natl. Acad. Sci. U. S. A. 95:1998;386.
81. Pan G., O'Rourke K., Dixit V.M. Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex. J. Biol. Chem. 273:1998;5841.
82. Conus S., Rosse T., Borner C. Failure of Bcl-2 family members to interact with Apaf-1 in normal and apoptotic cells. Cell Death Differ. 7:2000;947.
83. Moriishi K., Huang D.C., Cory S., Adams J.M. Bcl-2 family members do not inhibit apoptosis by binding the caspase activator Apaf-1. Proc. Natl. Acad. Sci. U. S. A. 96:1999;9683.
84. Foyouzi-Youssefi R., Arnaudeau S., Borner C., Kelley W.L., Tschopp J., Lew D.P., Demaurex N., Krause K.H. Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum. Proc. Natl. Acad. Sci. U. S. A. 97:2000;5723.
85. Zornig M., Busch G., Beneke R., Gulbins E., Lang F., Ma A., Korsmeyer S., Moroy T. Survival and death of prelymphomatous B-cells from N-myc/bcl-2 double transgenic mice correlates with the regulation of intracellular Ca2+ fluxes. Oncogene. 11:1995;2165.
86. Hacki J., Egger L., Monney L., Conus S., Rosse T., Fellay I., Borner C. Apoptotic crosstalk between the endoplasmic reticulum and mitochondria controlled by Bcl-2. Oncogene. 19:2000;2286.
87. Jiang M., Milner J. Bcl-2 constitutively suppresses p53-dependent apoptosis in colorectal cancer cells. Genes Dev. 17:2003;832.
88. Miyashita T., Harigai M., Hanada M., Reed J.C. Identification of a p53-dependent negative response element in the bcl-2 gene. Cancer Res. 54:1994;3131.
89. McDonnell T.J., Deane N., Platt F.M., Nunez G., Jaeger U., McKearn J.P., Korsmeyer S.J. bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell. 57:1989;79.
90. McDonnell T.J., Korsmeyer S.J. Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14; 18). Nature. 349:1991;254.
91. Adams J.M., Harris A.W., Pinkert C.A., Corcoran L.M., Alexander W.S., Cory S., Palmiter R.D., Brinster R.L. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature. 318:1985;533.
92. Strasser A., Harris A.W., Bath M.L., Cory S. Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. Nature. 348:1990;331.
93. Jager R., Herzer U., Schenkel J., Weiher H. Overexpression of Bcl-2 inhibits alveolar cell apoptosis during involution and accelerates c-myc-induced tumorigenesis of the mammary gland in transgenic mice. Oncogene. 15:1997;1787.
94. Bruckheimer E.M., Brisbay S., Johnson D.J., Gingrich J.R., Greenberg N., McDonnell T.J. Bcl-2 accelerates multistep prostate carcinogenesis in vivo. Oncogene. 19:2000;5251.
95. Kogan S.C., Brown D.E., Shultz D.B., Truong B.T., Lallemand-Breitenbach V., Guillemin M.C., Lagasse E., Weissman I.L., Bishop J.M. BCL-2 cooperates with promyelocytic leukemia retinoic acid receptor alpha chimeric protein (PMLRARalpha) to block neutrophil differentiation and initiate acute leukemia. J. Exp. Med. 193:2001;531.
96. Cleary M., Rosenberg S.A. The bcl-2 gene, follicular lymphoma, and Hodgkin's disease. J. Natl. Cancer Inst. 82:1990;808.
97. Horning S.J., Rosenberg S.A. The natural history of initially untreated low-grade non-Hodgkin's lymphomas. N. Engl. J. Med. 311:1984;1471.
98. Portlock C.S., Rosenberg S.A. No initial therapy for stage III and IV non-Hodgkin's lymphomas of favorable histologic types. Ann. Intern. Med. 90:1979;10.
99. Limpens J., de Jong D., van Krieken J.H., Price C.G., Young B.D., van Ommen G.J., Kluin P.M. Bcl-2/JH rearrangements in benign lymphoid tissues with follicular hyperplasia. Oncogene. 6:1991;2271.
100. Limpens J., Stad R., Vos C., de Vlaam C., de Jong D., van Ommen G.J., Schuuring E., Kluin P.M. Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals. Blood. 85:1995;2528.
101. Ayhan A., Yasui W., Yokozaki H., Seto M., Ueda R., Tahara E. Loss of heterozygosity at the bcl-2 gene locus and expression of bcl-2 in human gastric and colorectal carcinomas. Jpn. J. Cancer Res. 85:1994;584.
102. Castle V.P., Heidelberger K.P., Bromberg J., Ou X., Dole M., Nunez G. Expression of the apoptosis-suppressing protein bcl-2, in neuroblastoma is associated with unfavorable histology and N-myc amplification. Am. J. Pathol. 143:1993;1543.
103. Coustan-Smith E., Kitanaka A., Pui C.H., McNinch L., Evans W.E., Raimondi S.C., Behm F.G., Arico M., Campana D. Clinical relevance of BCL-2 overexpression in childhood acute lymphoblastic leukemia. Blood. 87:1996;1140.
104. Gobe G., Rubin M., Williams G., Sawczuk I., Buttyan R. Apoptosis and expression of Bcl-2, Bcl-XL, and Bax in renal cell carcinomas. Cancer Invest. 20:2002;324.
105. Kondo E., Yoshino T., Yamadori I., Matsuo Y., Kawasaki N., Minowada J., Akagi T. Expression of Bcl-2 protein and Fas antigen in non-Hodgkin's lymphomas. Am. J. Pathol. 145:1994;330.
106. Krajewska M., Krajewski S., Epstein J.I., Shabaik A., Sauvageot J., Song K., Kitada S., Reed J.C. Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers. Am. J. Pathol. 148:1996;1567.
107. Malkinson A.M. Molecular comparison of human and mouse pulmonary adenocarcinomas. Exp. Lung Res. 24:1998;541.
108. Zaja F., Di Loreto C., Amoroso V., Salmaso F., Russo D., Silvestri F., Fanin R., Damiani D., Infanti L., Mariuzzi L., Beltrami C.A., Baccarani M. BCL-2 immunohistochemical evaluation in B-cell chronic lymphocytic leukemia and hairy cell leukemia before treatment with fludarabine and 2-chloro-deoxy- adenosine. Leuk. Lymphoma. 28:1998;567.
109. Casado S., Forteza J., Dominguez S., Abad M.T., Perez I., Intxaurbe I., del Campo J.M., Lopez R. Predictive value of P53, BCL-2, and BAX in advanced head and neck carcinoma. Am. J. Clin. Oncol. 25:2002;588.
110. Gradilone A., Gazzaniga P., Ribuffo D., Scarpa S., Cigna E., Vasaturo F., Bottoni U., Innocenzi D., Calvieri S., Scuderi N., Frati L., Agliano A.M. Survivin, bcl-2, bax, and bcl-X gene expression in sentinel lymph nodes from melanoma patients. J. Clin. Oncol. 21:2003;306.
111. Stavropoulos N.E., Filiadis I., Ioachim E., Hastazeris K., Tsimaris I., Kalogeras D., Stefanaki S., Agnantis N.J. Prognostic significance of p53, bcl-2 and Ki-67 in high risk superficial bladder cancer. Anticancer Res. 22:2002;3759.
112. Chang J., Clark G.M., Allred D.C., Mohsin S., Chamness G., Elledge R.M. Survival of patients with metastatic breast carcinoma: importance of prognostic markers of the primary tumor. Cancer. 97:2003;545.
113. Pierce R.H., Vail M.E., Ralph L., Campbell J.S., Fausto N. Bcl-2 expression inhibits liver carcinogenesis and delays the development of proliferating foci. Am. J. Pathol. 160:2002;1555.
114. Eischen C.M., Packham G., Nip J., Fee B.E., Hiebert S.W., Zambetti G.P., Cleveland J.L. Bcl-2 is an apoptotic target suppressed by both c-Myc and E2F-1. Oncogene. 20:2001;6983.
115. Boise L.H., Gonzalez-Garcia M., Postema C.E., Ding L., Lindsten T., Turka L.A., Mao X., Nunez G., Thompson C.B. bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell. 74:1993;597.
116. Ma A., Pena J.C., Chang B., Margosian E., Davidson L., Alt F.W., Thompson C.B. Bclx regulates the survival of double-positive thymocytes. Proc. Natl. Acad. Sci. U. S. A. 92:1995;4763.
117. Peter M.E., Kischkel F.C., Scheuerpflug C.G., Medema J.P., Debatin K.M., Krammer P.H. Resistance of cultured peripheral T cells towards activation-induced cell death involves a lack of recruitment of FLICE (MACH/caspase 8) to the CD95 death-inducing signaling complex. Eur. J. Immunol. 27:1997;1207.
118. Motoyama N., Wang F., Roth K.A., Sawa H., Nakayama K., Negishi I., Senju S., Zhang Q., Fujii S.et al. Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice. Science. 267:1995;1506.
119. Zamzami N., Brenner C., Marzo I., Susin S.A., Kroemer G. Subcellular and submitochondrial mode of action of Bcl-2-like oncoproteins. Oncogene. 16:1998;2265.
120. Watanabe J., Kushihata F., Honda K., Mominoki K., Matsuda S., Kobayashi N. Bcl-xL overexpression in human hepatocellular carcinoma. Int. J. Oncol. 21:2002;515.
121. Ghaneh P., Kawesha A., Evans J.D., Neoptolemos J.P. Molecular prognostic markers in pancreatic cancer. J. Hepatobiliary Pancr. Surg. 9:2002;1.
122. Naik P., Karrim J., Hanahan D. The rise and fall of apoptosis during multistage tumorigenesis: down-modulation contributes to tumor progression from angiogenic progenitors. Genes Dev. 10:1996;2105.
123. Pena J.C., Rudin C.M., Thompson C.B. A Bcl-xL transgene promotes malignant conversion of chemically initiated skin papillomas. Cancer Res. 58:1998;2111.
124. Gibson L., Holmgreen S.P., Huang D.C., Bernard O., Copeland N.G., Jenkins N.A., Sutherland G.R., Baker E., Adams J.M., Cory S. bcl-w, a novel member of the bcl-2 family, promotes cell survival. Oncogene. 13:1996;665.
125. Denisov A.Y., Madiraju M.S., Chen G., Khadir A., Beauparlant P., Attardo G., Shore G.C., Gehring K. Solution structure of human BCL-w: modulation of ligand binding by the C-terminal helix. J. Biol. Chem. 21:2003;21.
126. Hinds M.G., Lackmann M., Skea G.L., Harrison P.J., Huang D.C., Day C.L. The structure of Bcl-w reveals a role for the C-terminal residues in modulating biological activity. EMBO J. 22:2003;1497.
127. O'Reilly L.A., Print C., Hausmann G., Moriishi K., Cory S., Huang D.C., Strasser A. Tissue expression and subcellular localization of the pro-survival molecule Bcl-w. Cell Death Differ. 8:2001;486.
128. Ross A.J., Waymire K.G., Moss J.E., Parlow A.F., Skinner M.K., Russell L.D., MacGregor G.R. Testicular degeneration in Bclw-deficient mice. Nat. Genet. 18:1998;251.
129. Wilson J.W., Nostro M.C., Balzi M., Faraoni P., Cianchi F., Becciolini A., Potten C.S. Bcl-w expression in colorectal adenocarcinoma. Br. J. Cancer. 82:2000;178.
130. Lee H.W., Lee S.S., Lee S.J., Um H.D. Bcl-w is expressed in a majority of infiltrative gastric adenocarcinomas and suppresses the cancer cell death by blocking stress-activated protein kinase/c-Jun NH2-terminal kinase activation. Cancer Res. 63:2003;1093.
131. Choi S.S., Park I.C., Yun J.W., Sung Y.C., Hong S.I., Shin H.S. A novel Bcl-2 related gene, Bfl-1, is overexpressed in stomach cancer and preferentially expressed in bone marrow. Oncogene. 11:1995;1693.
132. Karsan A., Yee E., Kaushansky K., Harlan J.M. Cloning of human Bcl-2 homologue: inflammatory cytokines induce human A1 in cultured endothelial cells. Blood. 87:1996;3089.
133. Werner A.B., de Vries E., Tait S.W., Bontjer I., Borst J. Bcl-2 family member Bfl-1/A1 sequesters truncated bid to inhibit is collaboration with pro-apoptotic Bak or Bax. J. Biol. Chem. 277:2002;22781.
134. Nieborowska-Skorska M., Hoser G., Kossev P., Wasik M.A., Skorski T. Complementary functions of the antiapoptotic protein A1 and serine/threonine kinase pim-1 in the BCR/ABL-mediated leukemogenesis. Blood. 99:2002;4531.
135. D'Sa-Eipper C., Subramanian T., Chinnadurai G. bfl-1, a bcl-2 homologue, suppresses p53-induced apoptosis and exhibits potent cooperative transforming activity. Cancer Res. 56:1996;3879.
136. Kozopas K.M., Yang T., Buchan H.L., Zhou P., Craig R.W. MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2. Proc. Natl. Acad. Sci. U. S. A. 90:1993;3516.
137. Zhou P., Qian L., Bieszczad C.K., Noelle R., Binder M., Levy N.B., Craig R.W. Mcl-1 in transgenic mice promotes survival in a spectrum of hematopoietic cell types and immortalization in the myeloid lineage. Blood. 92:1998;3226.
138. Zhang B., Gojo I., Fenton R.G. Myeloid cell factor-1 is a critical survival factor for multiple myeloma. Blood. 99:2002;1885.
139. Derenne S., Monia B., Dean N.M., Taylor J.K., Rapp M.J., Harousseau J.L., Bataille R., Amiot M. Antisense strategy shows that Mcl-1 rather than Bcl-2 or Bcl-x(L) is an essential survival protein of human myeloma cells. Blood. 100:2002;194.
140. Kitada S., Andersen J., Akar S., Zapata J.M., Takayama S., Krajewski S., Wang H.G., Zhang X., Bullrich F., Croce C.M., Rai K., Hines J., Reed J.C. Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with In vitro and In vivo chemoresponses. Blood. 91:1998;3379.
141. Kaufmann S.H., Karp J.E., Svingen P.A., Krajewski S., Burke P.J., Gore S.D., Reed J.C. Elevated expression of the apoptotic regulator Mcl-1 at the time of leukemic relapse. Blood. 91:1998;991.
142. Ma Y., Cress W.D., Haura E.B. Flavopiridol-induced apoptosis is mediated through up-regulation of E2F1 and repression of Mcl-1. Mol. Cancer Ther. 2:2003;73.
143. Mihara M., Shintani S., Nakashiro K., Hamakawa H. Flavopiridol, a cyclin dependent kinase (CDK) inhibitor, induces apoptosis by regulating Bcl-x in oral cancer cells. Oral Oncol. 39:2003;49.
144. Antonsson B., Montessuit S., Sanchez B., Martinou J.C. Bax is present as a high molecular weight oligomer/complex in the mitochondrial membrane of apoptotic cells. J. Biol. Chem. 276:2001;11615.
145. Mikhailov V., Mikhailova M., Degenhardt K., Venkatachalam M.A., White E., Saikumar P. Association of Bax and Bak homo-oligomers in mitochondria. Bax requirement for Bak reorganization and cytochrome c release. J. Biol. Chem. 278:2003;5367.
146. Nechushtan A., Smith C.L., Lamensdorf I., Yoon S.H., Youle R.J. Bax and Bak coalesce into novel mitochondria-associated clusters during apoptosis. J. Cell Biol. 153:2001;1265.
147. Knudson C.M., Tung K.S., Tourtellotte W.G., Brown G.A., Korsmeyer S.J. Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science. 270:1995;96.
148. Scorrano L., Oakes S.A., Opferman J.T., Cheng E.H., Sorcinelli M.D., Pozzan T., Korsmeyer S.J. BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science. 300:2003;135.
149. Yin C., Knudson C.M., Korsmeyer S.J., Van Dyke T. Bax suppresses tumorigenesis and stimulates apoptosis in vivo. Nature. 385:1997;637.
150. Shibata M.A., Liu M.L., Knudson M.C., Shibata E., Yoshidome K., Bandey T., Korsmeyer S.J., Green J.E. Haploid loss of bax leads to accelerated mammary tumor development in C3(1)/SV40-TAg transgenic mice: reduction in protective apoptotic response at the preneoplastic stage. EMBO J. 18:1999;2692.
151. McCurrach M.E., Connor T.M., Knudson C.M., Korsmeyer S.J., Lowe S.W. bax-deficiency promotes drug resistance and oncogenic transformation by attenuating p53-dependent apoptosis. Proc. Natl. Acad. Sci. U. S. A. 94:1997;2345.
152. Ravi R., Bedi A. Requirement of BAX for TRAIL/Apo2L-induced apoptosis of colorectal cancers: synergism with sulindac-mediated inhibition of Bcl-x(L). Cancer Res. 62:2002;1583.
153. LeBlanc H., Lawrence D., Varfolomeev E., Totpal K., Morlan J., Schow P., Fong S., Schwall R., Sinicropi D., Ashkenazi A. Tumor-cell resistance to death receptor-induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax. Nat. Med. 8:2002;274.
154. Kandasamy K., Srinivasula S.M., Alnemri E.S., Thompson C.B., Korsmeyer S.J., Bryant J.L., Srivastava R.K. Involvement of proapoptotic molecules Bax and Bak in Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-induced mitochondrial disruption and apoptosis: differential regulation of cytochrome c and Smac/DIABLO release. Cancer Res. 63:2003;1712.
155. Theodorakis P., Lomonosova E., Chinnadurai G. Critical requirement of BAX for manifestation of apoptosis induced by multiple stimuli in human epithelial cancer cells. Cancer Res. 62:2002;3373.
156. Degenhardt K., Sundararajan R., Lindsten T., Thompson C., White E. Bax and Bak independently promote cytochrome C release from mitochondria. J. Biol. Chem. 277:2002;14127.
157. Degenhardt K., Chen G., Lindsten T., White E. BAX and BAK mediate p53-independent suppression of tumorigenesis. Cancer Cells. 2:2002;193.
158. Eischen C.M., Roussel M.F., Korsmeyer S.J., Cleveland J.L. Bax loss impairs Myc-induced apoptosis and circumvents the selection of p53 mutations during Myc-mediated lymphomagenesis. Mol. Cell. Biol. 21:2001;7653.
159. Bargou R.C., Wagener C., Bommert K., Mapara M.Y., Daniel P.T., Arnold W., Dietel M., Guski H., Feller A., Royer H.D., Dorken B. Overexpression of the death-promoting gene bax-alpha which is downregulated in breast cancer restores sensitivity to different apoptotic stimuli and reduces tumor growth in SCID mice. J. Clin. Invest. 97:1996;2651.
160. Beerheide W., Tan Y.J., Teng E., Ting A.E., Jedpiyawongse A., Srivatanakul P. Downregulation of proapoptotic proteins Bax and Bcl-X(S) in p53 overexpressing hepatocellular carcinomas. Biochem. Biophys. Res. Commun. 273:2000;54.
161. Pepper C., Thomas A., Hoy T., Bentley P. Chlorambucil resistance in B-cell chronic lymphocytic leukaemia is mediated through failed Bax induction and selection of high Bcl-2-expressing subclones. Br. J. Haematol. 104:1999;581.
162. Rampino N., Yamamoto H., Ionov Y., Li Y., Sawai H., Reed J.C., Perucho M. Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science. 275:1997;967.
163. Meijerink J.P., Mensink E.J., Wang K., Sedlak T.W., Sloetjes A.W., de Witte T., Waksman G., Korsmeyer S.J. Hematopoietic malignancies demonstrate loss-of-function mutations of BAX. Blood. 91:1998;2991.
164. Mrozek A., Petrowsky H., Sturm I., Kraus J., Hermann S., Hauptmann S., Lorenz M., Dorken B., Daniel P.T. Combined p53/Bax mutation results in extremely poor prognosis in gastric carcinoma with low microsatellite instability. Cell Death Differ. 10:2003;461.
165. Prokop A., Wieder T., Sturm I., Essmann F., Seeger K., Wuchter C., Ludwig W.D., Henze G., Dorken B., Daniel P.T. Relapse in childhood acute lymphoblastic leukemia is associated with a decrease of the Bax/Bcl-2 ratio and loss of spontaneous caspase-3 processing in vivo. Leukemia. 14:2000;1606.
166. Schelwies K., Sturm I., Grabowski P., Scherubl H., Schindler I., Hermann S., Stein H., Buhr H.J., Riecken E.O., Zeitz M., Dorken B., Daniel P.T.
167. Sturm I., Kohne C.H., Wolff G., Petrowsky H., Hillebrand T., Hauptmann S., Lorenz M., Dorken B., Daniel P.T. Analysis of the p53/BAX pathway in colorectal cancer: low BAX is a negative prognostic factor in patients with resected liver metastases. J. Clin. Oncol. 17:1999;1364.
168. Sturm I., Petrowsky H., Volz R., Lorenz M., Radetzki S., Hillebrand T., Wolff G., Hauptmann S., Dorken B., Daniel P.T. Analysis of p53/BAX/p16(ink4a/ CDKN2) in esophageal squamous cell carcinoma: high BAX and p16(ink4a/CDKN2) identifies patients with good prognosis. J. Clin. Oncol. 19:2001;2272.
169. Rosen K., Rak J., Jin J., Kerbel R.S., Newman M.J., Filmus J. Downregulation of the pro-apoptotic protein Bak is required for the ras-induced transformation of intestinal epithelial cells. Curr. Biol. 8:1998;1331.
170. Kondo S., Shinomura Y., Miyazaki Y., Kiyohara T., Tsutsui S., Kitamura S., Nagasawa Y., Nakahara M., Kanayama S., Matsuzawa Y. Mutations of the bak gene in human gastric and colorectal cancers. Cancer Res. 60:2000;4328.
171. Boudard D., Vasselon C., Bertheas M.F., Jaubert J., Mounier C., Reynaud J., Viallet A., Chautard S., Guyotat D., Campos L. Expression and prognostic significance of Bcl-2 family proteins in myelodysplastic syndromes. Am. J. Hematol. 70:2002;115.
172. Yamaguchi H., Inokuchi K., Dan K. The study for loss of bcl-xs expression as a prognostic factor in acute myeloid leukemia. Leuk. Res. 26:2002;1119.
173. Clarke M.F., Apel I.J., Benedict M.A., Eipers P.G., Sumantran V., Gonzalez-Garcia M., Doedens M., Fukunaga N., Davidson B., Dick J.E.et al. A recombinant bcl-x s adenovirus selectively induces apoptosis in cancer cells but not in normal bone marrow cells. Proc. Natl. Acad. Sci. U. S. A. 92:1995;11024.
174. Dole M.G., Clarke M.F., Holman P., Benedict M., Lu J., Jasty R., Eipers P., Thompson C.B., Rode C., Bloch C., Castle V.P. Bcl-xS enhances adenoviral vector-induced apoptosis in neuroblastoma cells. Cancer Res. 56:1996;5734.
175. Ealovega M.W., McGinnis P.K., Sumantran V.N., Clarke M.F., Wicha M.S. bcl-xs gene therapy induces apoptosis of human mammary tumors in nude mice. Cancer Res. 56:1996;1965.
176. Sumantran V.N., Lee D.S., Woods Ignatoski K.M., Ethier S.P., Wicha M.S. A bcl-xS adenovirus selectively induces apoptosis in transformed cells compared to normal mammary cells. Neoplasia. 2:2000;251.
177. Sanz C., Benito A., Inohara N., Ekhterae D., Nunez G., Fernandez-Luna J.L. Specific and rapid induction of the proapoptotic protein Hrk after growth factor withdrawal in hematopoietic progenitor cells. Blood. 95:2000;2742.
178. Lutter M., Fang M., Luo X., Nishijima M., Xie X., Wang X. Cardiolipin provides specificity for targeting of tBid to mitochondria. Nat. Cell Biol. 2:2000;754.
179. Zinkel S.S., Ong C.C., Ferguson D.O., Iwasaki H., Akashi K., Bronson R.T., Kutok J.L., Alt F.W., Korsmeyer S.J. Proapoptotic BID is required for myeloid homeostasis and tumor suppression. Genes Dev. 17:2003;229.
180. Panaretakis T., Pokrovskaja K., Shoshan M.C., Grander D. Activation of Bak, Bax, and BH3-only proteins in the apoptotic response to doxorubicin. J. Biol. Chem. 277:2002;44317.
181. Mandic A., Viktorsson K., Strandberg L., Heiden T., Hansson J., Linder S., Shoshan M.C. Calpain-mediated Bid cleavage and calpain-independent Bak modulation: two separate pathways in cisplatin-induced apoptosis. Mol. Cell. Biol. 22:2002;3003.
182. Borner C. Diminished cell proliferation associated with the death-protective activity of Bcl-2. J. Biol. Chem. 271:1996;12695.
183. Linette G.P., Li Y., Roth K., Korsmeyer S.J. Cross talk between cell death and cell cycle progression: BCL-2 regulates NFAT-mediated activation. Proc. Natl. Acad. Sci. U. S. A. 93:1996;9545.
184. Mazel S., Burtrum D., Petrie H.T. Regulation of cell division cycle progression by bcl-2 expression: a potential mechanism for inhibition of programmed cell death. J. Exp. Med. 183:1996;2219.
185. O'Reilly L.A., Huang D.C., Strasser A. The cell death inhibitor Bcl-2 and its homologues influence control of cell cycle entry. EMBO J. 15:1996;6979.
186. Huang D.C., O'Reilly L.A., Strasser A., Cory S. The anti-apoptosis function of Bcl-2 can be genetically separated from its inhibitory effect on cell cycle entry. EMBO J. 16:1997;4628.
187. Vairo G., Innes K.M., Adams J.M. Bcl-2 has a cell cycle inhibitory function separable from its enhancement of cell survival. Oncogene. 13:1996;1511.
188. Brady H.J., Gil-Gomez G., Kirberg J., Berns A.J. Bax alpha perturbs T cell development and affects cell cycle entry of T cells. EMBO J. 15:1996;6991.
189. Knudson C.M., Johnson G.M., Lin Y., Korsmeyer S.J. Bax accelerates tumorigenesis in p53-deficient mice. Cancer Res. 61:2001;659.
190. Murphy K.L., Kittrell F.S., Gay J.P., Jager R., Medina D., Rosen J.M. Bcl-2 expression delays mammary tumor development in dimethylbenz(a)anthracene- treated transgenic mice. Oncogene. 18:1999;6597.
191. de La Coste A., Mignon A., Fabre M., Gilbert E., Porteu A., Van Dyke T., Kahn A., Perret C. Paradoxical inhibition of c-myc-induced carcinogenesis by Bcl-2 in transgenic mice. Cancer Res. 59:1999;5017.
192. Kuwashima Y., Kobayashi Y., Kurosumi M., Tanuma J., Shiromizu K., Kishi K. Inverse correlation between bcl-2 expression and cell growth fraction in human endometrial adenocarcinoma tissue. Anticancer Res. 17:1997;3773.
193. Limana F., Urbanek K., Chimenti S., Quaini F., Leri A., Kajstura J., Nadal-Ginard B., Izumo S., Anversa P. bcl-2 overexpression promotes myocyte proliferation. Proc. Natl. Acad. Sci. U. S. A. 99:2002;6257.
194. Furth P.A., Bar-Peled U., Li M., Lewis A., Laucirica R., Jager R., Weiher H., Russell R.G. Loss of anti-mitotic effects of Bcl-2 with retention of anti-apoptotic activity during tumor progression in a mouse model. Oncogene. 18:1999;6589.
195. Matolcsy A., Casali P., Warnke R.A., Knowles D.M. Morphologic transformation of follicular lymphoma is associated with somatic mutation of the translocated Bcl-2 gene. Blood. 88:1996;3937.
196. Uhlmann E.J., D'Sa-Eipper C., Subramanian T., Wagner A.J., Hay N., Chinnadurai G. Deletion of a nonconserved region of Bcl-2 confers a novel gain of function: suppression of apoptosis with concomitant cell proliferation. Cancer Res. 56:1996;2506.
197. Gil-Gomez G., Berns A., Brady H.J. A link between cell cycle and cell death: Bax and Bcl-2 modulate Cdk2 activation during thymocyte apoptosis. EMBO J. 17:1998;7209.
198. Greider C., Chattopadhyay A., Parkhurst C., Yang E. BCL-x(L) and BCL2 delay Myc-induced cell cycle entry through elevation of p27 and inhibition of G1 cyclin-dependent kinases. Oncogene. 21:2002;7765.
199. Fujise K., Zhang D., Liu J., Yeh E.T. Regulation of apoptosis and cell cycle progression by MCL1. Differential role of proliferating cell nuclear antigen. J. Biol. Chem. 275:2000;39458.
200. Johnstone R.W., Ruefli A.A., Lowe S.W. Apoptosis: a link between cancer genetics and chemotherapy. Cell. 108:2002;153.
201. Buchholz T.A., Davis D.W., McConkey D.J., Symmans W.F., Valero V., Jhingran A., Tucker S.L., Pusztai L., Cristofanilli M., Esteva F.J., Hortobagyi G.N., Sahin A.A. Chemotherapy-induced apoptosis and Bcl-2 levels correlate with breast cancer response to chemotherapy. Cancer J. 9:2003;33.
202. Marriott J.B., Clarke I.A., Czajka A., Dredge K., Childs K., Man H.W., Schafer P., Govinda S., Muller G.W., Stirling D.I., Dalgleish A.G. A novel subclass of thalidomide analogue with anti-solid tumor activity in which caspase-dependent apoptosis is associated with altered expression of bcl-2 family proteins. Cancer Res. 63:2003;593.
203. Mounier N., Briere J., Gisselbrecht C., Emile J.F., Lederlin P., Sebban C., Berger F., Bosly A., Morel P., Tilly H., Bouabdallah R., Reyes F., Gaulard P., Coiffier B. Rituximab plus CHOP (R-CHOP) overcomes bcl-2-associated resistance to chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL). Blood. 6:2003;6.
204. Pepper C., Hoy T., Bentley P. Elevated Bcl-2/Bax are a consistent feature of apoptosis resistance in B-cell chronic lymphocytic leukaemia and are correlated with in vivo chemoresistance. Leuk. Lymphoma. 28:1998;355.
205. Reed J.C. Dysregulation of apoptosis in cancer. J. Clin. Oncol. 17:1999;2941.
206. Schmitt C.A., Rosenthal C.T., Lowe S.W. Genetic analysis of chemoresistance in primary murine lymphomas. Nat. Med. 6:2000;1029.
207. Wei M.C., Zong W.X., Cheng E.H., Lindsten T., Panoutsakopoulou V., Ross A.J., Roth K.A., MacGregor G.R., Thompson C.B., Korsmeyer S.J. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science. 292:2001;727.
208. Zhang L., Yu J., Park B.H., Kinzler K.W., Vogelstein B. Role of BAX in the apoptotic response to anticancer agents. Science. 290:2000;989.
209. Condon L.T., Ashman J.N., Ell S.R., Stafford N.D., Greenman J., Cawkwell L. Overexpression of Bcl-2 in squamous cell carcinoma of the larynx: a marker of radioresistance. Int. J. Cancer. 100:2002;472.
210. Gilbert M.S., Saad A.H., Rupnow B.A., Knox S.J. Association of BCL-2 with membrane hyperpolarization and radioresistance. J. Cell. Physiol. 168:1996;114.
211. Kariya S., Ogawa Y., Yoshida S., Yabuki M., Imajo Y., Utsumi K. X-irradiation enhances the expression of Bcl-2 in HL-60 cells: the resulting effects on apoptosis and radiosensitivity. Int. J. Mol. Med. 3:1999;145.
212. Lee J.U., Hosotani R., Wada M., Doi R., Kosiba T., Fujimoto K., Miyamoto Y., Tsuji S., Nakajima S., Nishimura Y., Imamura M. Role of Bcl-2 family proteins (Bax, Bcl-2 and Bcl-X) on cellular susceptibility to radiation in pancreatic cancer cells. Eur. J. Cancer. 35:1999;1374.
213. Vogelstein B., Lane D., Levine A.J. Surfing the p53 network. Nature. 408:2000;307.
214. INK4a contributes to the outcome of cancer therapy. Cell. 109:2002;335.
215. Chi K.C., Wallis A.E., Lee C.H., De Menezes D.L., Sartor J., Dragowska H., Mayer L.D. Effects of Bcl-2 modulation with G3139 antisense oligonucleotide on human breast cancer cells are independent of inherent Bcl-2 protein expression. Breast Cancer Res. Treat. 63:2000;199.
216. Lopes D., Mayer L.D. Pharmacokinetics of Bcl-2 antisense oligonucleotide (G3139) combined with doxorubicin in SCID mice bearing human breast cancer solid tumor xenografts. Cancer Chemother. Pharmacol. 49:2002;57.
217. Schlagbauer-Wadl H., Klosner G., Heere-Ress E., Waltering S., Moll I., Wolff K., Pehamberger H., Jansen B. Bcl-2 antisense oligonucleotides (G3139) inhibit Merkel cell carcinoma growth in SCID mice. J. Invest. Dermatol. 114:2000;725.
218. Waters J.S., Webb A., Cunningham D., Clarke P.A., Raynaud F., di Stefano F., Cotter F.E. Phase I clinical and pharmacokinetic study of bcl-2 antisense oligonucleotide therapy in patients with non-Hodgkin's lymphoma. J. Clin. Oncol. 18:2000;1812.
219. Klasa R.J., Gillum A.M., Klem R.E., Frankel S.R. Oblimersen Bcl-2 antisense: facilitating apoptosis in anticancer treatment. Antisense Nucleic Acid Drug Dev. 12:2002;193.
220. Olie R.A., Hafner C., Kuttel R., Sigrist B., Willers J., Dummer R., Hall J., Stahel R.A., Zangemeister-Wittke U. Bcl-2 and bcl-xL antisense oligonucleotides induce apoptosis in melanoma cells of different clinical stages. J. Invest. Dermatol. 118:2002;505.
221. Heere-Ress E., Thallinger C., Lucas T., Schlagbauer-Wadl H., Wacheck V., Monia B.P., Wolff K., Pehamberger H., Jansen B. Bcl-X(L) is a chemoresistance factor in human melanoma cells that can be inhibited by antisense therapy. Int. J. Cancer. 99:2002;29.
222. Mercatante D.R., Mohler J.L., Kole R. Cellular response to an antisense-mediated shift of Bcl-x pre-mRNA splicing and antineoplastic agents. J. Biol. Chem. 277:2002;49374.
223. Gautschi O., Tschopp S., Olie R.A., Leech S.H., Simoes-Wust A.P., Ziegler A., Baumann B., Odermatt B., Hall J., Stahel R.A., Zangemeister-Wittke U. Activity of a novel bcl-2/bcl-xL-bispecific antisense oligonucleotide against tumors of diverse histologic origins. J. Natl. Cancer Inst. 93:2001;463.
224. Jiang Z., Zheng X., Rich K.M. Down-regulation of Bcl-2 and Bcl-xL expression with bispecific antisense treatment in glioblastoma cell lines induce cell death. J. Neurochem. 84:2003;273.
225. Zangemeister-Wittke U., Leech S.H., Olie R.A., Simoes-Wust A.P., Gautschi O., Luedke G.H., Natt F., Haner R., Martin P., Hall J., Nalin C.M., Stahel R.A. A novel bispecific antisense oligonucleotide inhibiting both bcl-2 and bcl-xL expression efficiently induces apoptosis in tumor cells. Clin. Cancer Res. 6:2000;2547.
226. Tanabe K., Kim R., Inoue H., Emi M., Uchida Y., Toge T. Antisense Bcl-2 and HER-2 oligonucleotide treatment of breast cancer cells enhances their sensitivity to anticancer drugs. Int. J. Oncol. 22:2003;875.
227. Elez R., Piiper A., Kronenberger B., Kock M., Brendel M., Hermann E., Pliquett U., Neumann E., Zeuzem S. Tumor regression by combination antisense therapy against Plk1 and Bcl-2. Oncogene. 22:2003;69.
228. Luzi E., Papucci L., Schiavone N., Donnini M., Lapucci A., Tempestini A., Witort E., Nicolin A., Capaccioli S. Downregulation of bcl-2 expression in lymphoma cells by bcl-2 ARE-targeted modified, synthetic ribozyme. Cancer Gene Ther. 10:2003;201.
229. Wang J.L., Zhang Z.J., Choksi S., Shan S., Lu Z., Croce C.M., Alnemri E.S., Korngold R., Huang Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 60:2000;1498.
230. Wang J.L., Liu D., Zhang Z.J., Shan S., Han X., Srinivasula S.M., Croce C.M., Alnemri E.S., Huang Z. Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. Proc. Natl. Acad. Sci. U. S. A. 97:2000;7124.
231. Finnegan N.M., Curtin J.F., Prevost G., Morgan B., Cotter T.G. Induction of apoptosis in prostate carcinoma cells by BH3 peptides which inhibit Bak/ Bcl-2 interactions. Br. J. Cancer. 85:2001;115.
232. Degterev A., Lugovskoy A., Cardone M., Mulley B., Wagner G., Mitchison T., Yuan J. Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL. Nat. Cell Biol. 3:2001;173.
233. Tzung S.P., Kim K.M., Basanez G., Giedt C.D., Simon J., Zimmerberg J., Zhang K.Y., Hockenbery D.M. Antimycin A mimics a cell-death-inducing Bcl-2 homology domain 3. Nat. Cell Biol. 3:2001;183.
234. Zheng T.S. Death by design: the big debut of small molecules. Nat. Cell Biol. 3:2001;43.
235. Lowe S.L., Rubinchik S., Honda T., McDonnell T.J., Dong J.Y., Norris J.S. Prostate-specific expression of Bax delivered by an adenoviral vector induces apoptosis in LNCaP prostate cancer cells. Gene Ther. 8:2001;1363.
236. Pataer A., Smythe W.R., Yu R., Fang B., McDonnell T., Roth J.A., Swisher S.G. Adenovirus-mediated Bak gene transfer induces apoptosis in mesothelioma cell lines. J. Thorac. Cardiovasc. Surg. 121:2001;61.
237. Sugimoto C., Fujieda S., Seki M., Sunaga H., Fan G.K., Tsuzuki H., Borner C., Saito H., Matsukawa S. Apoptosis-promoting gene (bax) transfer potentiates sensitivity of squamous cell carcinoma to cisplatin in vitro and in vivo. Int. J. Cancer. 82:1999;860.
238. Cosulich S.C., Worrall V., Hedge P.J., Green S., Clarke P.R. Regulation of apoptosis by BH3 domains in a cell-free system. Curr. Biol. 7:1997;913.
239. Holinger E.P., Chittenden T., Lutz R.J. Bak BH3 peptides antagonize Bcl-xL function and induce apoptosis through cytochrome c-independent activation of caspases. J. Biol. Chem. 274:1999;13298.
240. Moreau C., Cartron P.F., Hunt A., Meflah K., Green D.R., Evan G., Vallette F.M., Juin P. Minimal BH3 peptides promote cell death by antagonizing anti-apoptotic proteins. J. Biol. Chem. 278:2003;19426.
241. Polster B.M., Kinnally K.W., Fiskum G. BH3 death domain peptide induces cell type-selective mitochondrial outer membrane permeability. J. Biol. Chem. 276:2001;37887.
242. Shangary S., Johnson D.E. Peptides derived from BH3 domains of Bcl-2 family members: a comparative analysis of inhibition of Bcl-2, Bcl-x(L) and Bax oligomerization, induction of cytochrome c release, and activation of cell death. Biochemistry. 41:2002;9485.
243. Vieira H.L., Boya P., Cohen I., El Hamel C., Haouzi D., Druillenec S., Belzacq A.S., Brenner C., Roques B., Kroemer G. Cell permeable BH3-peptides overcome the cytoprotective effect of Bcl-2 and Bcl-X(L). Oncogene. 21:2002;1963.
244. Ogasawara J., Watanabe-Fukunaga R., Adachi M., Matsuzawa A., Kasugai T., Kitamura Y., Itoh N., Suda T., Nagata S. Lethal effect of the anti-Fas antibody in mice. Nature. 364:1993;806.
245. Berrar D., Dubitzky W., Solinas-Toldo S., Bulashevska S., Granzow M., Conrad C., Kalla J., Lichter P., Eils R. A database system for comparative genomic hybridization analysis. IEEE Eng. Med. Biol. Mag. 20:2001;75.