Oncogenes as novel targets for cancer therapy (part II): Intermediate signaling molecules

American Journal of PharmacoGenomics

Volumn 5, Issue 4, 2005, Pages 247-257

  Zhang, Zhuo ^a   Li, Mao ^a   Rayburn, Elizabeth R ^a   Hill, Donald L ^a,b   Zhang, Ruiwen ^a,b,c   Wang, Hui ^a,b,d  

^a Clinical Nutrition Research Center   (United States)

^b Department of Pharmacology and Toxicology and Mass Spectrometry Core Facility   (United States)

^c UNIVERSITY OF ALABAMA SCHOOL OF MEDICINE   (United States)

^d University of Alabama at Birmingham   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; ADAPHOSTIN; ANTISENSE OLIGONUCLEOTIDE; APTAMER; CGP 69846A; COUMAMYCIN; CYCLIC AMP DEPENDENT PROTEIN KINASE; DOCETAXEL; EDELFOSINE; EVEROLIMUS; GELDANAMYCIN; GROWTH FACTOR; ISIS 2503; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; PACLITAXEL; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; PROTEIN KINASE (CALCIUM,CALMODULIN); PROTEIN KINASE B; PROTEIN KINASE INHIBITOR; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; RAF PROTEIN; RAPAMYCIN; RAS PROTEIN; SORAFENIB; TAXANE DERIVATIVE; TEMSIROLIMUS; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; WORTMANNIN; DNA;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CANCER GENETICS; CANCER THERAPY; CARCINOGENESIS; CELL CYCLE REGULATION; CLINICAL TRIAL; DNA DAMAGE; DNA REPAIR; DRUG DESIGN; DRUG MECHANISM; DRUG POTENTIATION; DRUG TARGETING; GENE FUNCTION; GENE IDENTIFICATION; GENE TARGETING; HUMAN; KIDNEY CARCINOMA; MELANOMA; NONHUMAN; ONCOGENE; ONCOGENE RAS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; T CELL LEUKEMIA; T CELL LYMPHOMA; TREATMENT OUTCOME; ANIMAL; GENE THERAPY; GENETICS; NEOPLASM; PATHOPHYSIOLOGY;

ANIMALS; DNA, NEOPLASM; GENE THERAPY; HUMANS; NEOPLASMS; ONCOGENES; SIGNAL TRANSDUCTION;

EID: 26944455228     PISSN: 11752203     EISSN: 11752203     Source Type: Journal    
DOI: 10.2165/00129785-200505040-00005     Document Type: Review

References (148)

1. Zhang Z, Li M, Rayburn ER, et al. Oncogenes as novel targets for cancer therapy (part I): growth factors and protein tyrosine kinases. Am J Pharmacogenomics 2005; 5 (3): 173-90
2. Smalley KS. A pivotal role for ERK in the oncogenic behavior of malignant melanoma? Int J Cancer 2003; 104: 527-32
3. McCormick F. Signal transduction: how receptors turn Ras on. Nature 1993; 363: 15-6
4. Kolch W. Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions. Biochem J 2000; 351: 289-305
5. Crews CM, Alessandrini A, Erikson RL. The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product. Science 1992; 258: 478-80
6. Kyriakis JM, App H, Zhang XF, et al. Raf-1 activates MAP kinase-kinase. Nature 1992; 358: 417-21
7. Treisman R. Ternary complex factors: growth factor regulated transcriptional activators. Curr Opin Genet Dev 1994; 4: 96-101
8. Mansour SJ, Matten WT, Hermann AS, et al. Transformation of mammalian cells by constitutively active MAP kinase kinase. Science 1994; 265: 966-70
9. Li T, Sparano JA. Inhibiting Ras signaling in the therapy of breast cancer. Clin Breast Cancer 2003; 3: 405-16
10. Lyons JF, Wilhelm S, Hibner B, et al. Discovery of a novel Raf kinase inhibitor. Endocr Relat Cancer 2001; 8: 219-25
11. Yan J, Roy S, Apolloni A, et al. Ras isoforms vary in their ability to activate Raf-1 and phosphoinositide 3-kinase. J Biol Chem 1998; 273: 24052-6
12. Steelman LS, Pohnert SC, Shelton JG, et al. JAK/STAT, Raf/MEK/ERK, PI3K/Akt and BCR-ABL in cell cycle progression and leukemogenesis. Leukemia 2004; 18: 189-218
13. Moodie SA, Wolfman A. The 3Rs of life: Ras, Raf and growth regulation. Trends Genet 1994; 10: 44-8
14. Mason CS, Springer CJ, Cooper RG, et al. Serine and tyrosine phosphorylations cooperate in Raf-1, but not B-Raf activation. EMBO J 1999; 18: 2137-48
15. Malliri AE, Collard JG. Role of Rho-family proteins in cell adhesion and cancer. Curr Opin Cell Biol 2003; 15: 583-9
16. Mertens AE, Roovers RC, Collard JG. Regulation of Tiam1-Rac signalling. FEBS Lett 2003; 546: 11-6
17. Sander EE, van Delft S, ten Klooster JP, et al. Matrix-dependent Tiam1/Rac signaling in epithelial cells promotes either cell-cell adhesion or cell migration and is regulated by phosphatidylinositol 3-kinase. J Cell Biol 1998; 143: 1385-98
18. Malliri A, van der Kammen RA, Clark K, et al. Mice deficient in the Rac activator Tiam1 are resistant to Ras-induced skin tumours. Nature 2002; 417: 867-71
19. Rowinsky EK, Windle JJ, Von Hoff DD. Ras protein farnesyltransferase: a strategic target for anticancer therapeutic development. J Clin Oncol 1999; 17: 3631-52
20. Oldham SM, Cox AD, Reynolds ER, et al. Ras, but not Src, transformation of RIE-1 epithelial cells is dependent on activation of the mitogen-activated protein kinase cascade. Oncogene 1998; 16: 2565-73
21. Yoshida T, Ohnami S, Aoki K. Development of gene therapy to target pancreatic cancer. Cancer Sci 2004; 95: 283-9
22. Raben D, Helfrich B, Bunn PA. Targeted therapies for non-small-cell lung cancer: biology, rationale, and preclinical results from a radiation oncology perspective. Int J Radiat Oncol Biol Phys 2004; 59 (2 Suppl.): 27-38
23. Perentesis JP, Bhatia S, Boyle E, et al. RAS oncogene mutations and outcome of therapy for childhood acute lymphoblastic leukemia. Leukemia 2004; 18: 685-92
24. Johnson L, Mercer K, Greenbaum D, et al. Somatic activation of the K-ras oncogene causes early onset lung cancer in mice. Nature 2001; 410: 1111-6
25. Adjei AA, Dy GK, Erlichman C, et al. A phase I trial of ISIS 2503, an antisense inhibitor of H-ras, in combination with gemcitabine in patients with advanced cancer. Clin Cancer Res 2003; 9: 115-23
26. Rak J, Yu JL. Oncogenes and tumor angiogenesis: the question of vascular "supply" and vascular "demand". Semin Cancer Biol 2004; 14: 93-104
27. Satyamoorthy K, Bogenrieder T, Herlyn M. No longer a molecular black box: new clues to apoptosis and drug resistance in melanoma. Trends Mol Med 2001; 7: 191-4
28. Lee JT, McCubrey JA. The Raf/MEK/ERK signal transduction cascade as a target for chemotherapeutic intervention in leukemia. Leukemia 2002; 16: 486-507
29. Halaschek-Wiener J, Kloog Y, Wacheck V, et al. Farnesyl thiosalicylic acid chemosensitizes human melanoma in vivo. J Invest Dermatol 2003; 120: 109-15
30. Dempke WC. Farnesyltransferase inhibitors: a novel approach in the treatment of advanced pancreatic carcinomas. Anticancer Res 2003; 23: 813-8
31. Ryan DP, Eder JP, Puchlaski T, et al. Phase I clinical trial of the farnesyltransferase inhibitor BMS-214662 given as a 1-hour intravenous infusion in patients with advanced solid tumors. Clin Cancer Res 2004; 10: 2222-30
32. Patnaik A, Eckhardt SG, Izbicka E, et al. A phase I, pharmacokinetic, and biological study of the farnesyltransferase inhibitor tipifarnib in combination with gemcitabine in patients with advanced malignancies. Clin Cancer Res 2003; 9: 4761-71
33. Alsina M, Fonseca R, Wilson EF, et al. Farnesyltransferase inhibitor tipifarnib is well tolerated, induces stabilization of disease, and inhibits farnesylation and oncogenic/tumor survival pathways in patients with advanced multiple myeloma. Blood 2004; 103: 3271-7
34. Bell IM. Inhibitors of farnesyltransferase: a rational approach to cancer chemotherapy? J Med Chem 2004; 47: 1869-78
35. McPherson RA, Conaway MC, Gregory CW, et al. The novel Ras antagonist, farnesylthiosalicylate, suppresses growth of prostate cancer in vitro. Prostate 2004; 58: 325-34
36. Johnson BE, Heymach JV. Farnesyl transferase inhibitors for patients with lung cancer. Clin Cancer Res 2004; 10 (12 Pt 2): 4254s-7s
37. Morioka CY, Saito S, Machado MC, et al. Antisense therapy specific to mutated K-ras gene in hamster pancreatic cancer model: can it inhibit the growth of 5-FU and MMC-resistant metastatic and remetastatic cell lines? In Vivo 2004; 18: 113-7
38. Cogoi S, Ballico M, Bonora GM, et al. Antiproliferative activity of a triplex-forming oligonucleotide recognizing a Ki-ras polypurine/polypyrimidine motif correlates with protein binding. Cancer Gene Ther 2004; 11: 465-76
39. Cogoi S, Quadrifoglio F, Xodo LE. G-rich oligonucleotide inhibits the binding of a nuclear protein to the Ki-ras promoter and strongly reduces cell growth in human carcinoma pancreatic cells. Biochemistry 2004; 43: 2512-23
40. Moelling K, Heimann B, Beimling P, et al. Serine- and threonine-specific protein kinase activities of purified gag-mil and gag-raf proteins. Nature 1984; 312: 558-61
41. Morrison DK, Cutler RE. The complexity of Raf-1 regulation. Curr Opin Cell Biol 1997; 9: 174-9
42. Pathan NI, Ashendel CL, Geahlen RL, et al. Activation of T cell Raf-1 at mitosis requires the protein-tyrosine kinase Lck. J Biol Chem 1996; 271: 30315-7
43. Farrar MA, Alberol-Ila, Perlmutter RM. Activation of the Raf-1 kinase cascade by coumermycin-induced dimerization. Nature 1996; 383: 178-81
44. Mikula M, Schreiber M, Husak Z, et al. Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene. EMBO J 2001; 20: 1952-62
45. Wang HG, Rapp UR, Reed JC. Bcl-2 targets the protein kinase Raf-1 to mitochondria. Cell 1996; 87: 629-38
46. Salomoni P, Wasik MA, Riedel RF, et al. Expression of constitutively active Raf-1 in the mitochondria restores antiapoptotic and leukemogenic potential of a transformation-deficient BCR/ABL mutant. J Exp Med 1998; 187: 1995-2007
47. Chang F, McCubrey JA. P21(Cip1) induced by Raf is associated with increased Cdk4 activity in hematopoietic cells. Oncogene 2001; 20: 4354-64
48. Chong H, Lee J, Guan KL. Positive and negative regulation of Raf kinase activity and function by phosphorylation. EMBO J 2001; 20: 3716-27
49. Hoyle PE, Moye PW, Steelman LS, et al. Differential abilities of the Raf family of protein kinases to abrogate cytokine dependency and prevent apoptosis in murine hematopoietic cells by a MEK1-dependent mechanism. Leukemia 2000; 14: 642-56
50. Bos JL. Ras oncogenes in human cancer: a review. Cancer Res 1989; 49: 4682-9
51. Storm SM, Rapp UR. Oncogene activation: c-raf-1 gene mutations in experimental and naturally occurring tumors. Toxicol Lett 1993; 67: 201-10
52. Hilger RA, Scheulen ME, Strumberg D. The Ras-Raf-MEK-ERK pathway in the treatment of cancer. Onkologie 2002; 25: 511-8
53. Bollag G, Freeman S, Lyons JF, et al. Raf pathway inhibitors in oncology. Curr Opin Investig Drugs 2003; 4: 1436-41
54. Pollock PM, Harper UL, Hansen KS, et al. High frequency of BRAF mutations in nevi. Nat Genet 2003; 33: 19-20
55. Dong J, Phelps RG, Qiao R, et al. BRAF oncogenic mutations correlate with progression rather than initiation of human melanoma. Cancer Res 2003; 63: 3883-5
56. Schulze A, Lehmann K, Jefferies HB, et al. Analysis of the transcriptional program induced by Raf in epithelial cells. Genes Dev 2001; 15: 981-94
57. Yu C, Rahmani M, Almenara J, et al. Induction of apoptosis in human leukemia cells by the tyrosine kinase inhibitor adaphostin proceeds through a RAF-1/MEK/ERK- and AKT-dependent process. Oncogene 2004; 23: 1364-76
58. Oza AM, Elit L, Swenerton K, et al. NCIC Clinical Trials Group Study (NCIC IND.116). Phase II study of CGP 69846A (ISIS 5132) in recurrent epithelial ovarian cancer: an NCIC clinical trials group study (NCIC IND.116). Gynecol Oncol 2003; 89: 129-33
59. Cioca DP, Aoki Y, Kiyosawa K. RNA interference is a functional pathway with therapeutic potential in human myeloid leukemia cell lines. Cancer Gene Ther 2003; 10: 125-33
60. Pei J, Zhang C, Gokhale PC, et al. Combination with liposome-entrapped, ends-modified raf antisense oligonucleotide (LErafAON) improves the anti-tumor efficacies of cisplatin, epirubicin, mitoxantrone, docetaxel and gemcitabine. Anticancer Drugs 2004; 15: 243-53
61. Kasid U, Dritschilo A. RAF antisense oligonucleotide as a tumor radiosensitizer. Oncogene 2003; 22: 5876-84
62. Richly H, Kupsch P, Passage K, et al. A phase I clinical and pharmacokinetic study of the Raf kinase inhibitor (RKI) BAY 43-9006 administered in combination with doxorubicin in patients with solid tumors. Int J Clin Pharmacol Ther 2003; 41: 620-1
63. Heim M, Sharifi M, Hilger RA, et al. Antitumor effect and potentiation or reduction in cytotoxic drug activity in human colon carcinoma cells by the Raf kinase inhibitor (RKI) BAY 43-9006. Int J Clin Pharmacol Ther 2003; 41: 616-7
64. Bisht KS, Bradbury CM, Mattson D, et al. Geldanamycin and 17-allylamino-17-demethoxygeldanamycin potentiate the in vitro and in vivo radiation response of cervical tumor cells via the heat shock protein 90-mediated intracellular signaling and cytotoxicity. Cancer Res 2003; 63: 8984-95
65. Samadder P, Richards C, Bittman R, et al. The antitumor ether lipid 1-Q-octadecyl-2-O-methyl-rac-glycerophosphocholine (ET-18-OCH3) inhibits the association between Ras and Raf-1. Anticancer Res 2003; 23: 2291-5
66. Pearson G, Robinson F, Beers Gibson T, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 2001; 22: 153-83
67. Blalock WL, Pearce M, Chang F, et al. Effects of inducible MEK1 activation on the cytokine dependency of lymphoid cells. Leukemia 2001; 15: 794-807
68. Yip-Schneider MT, Schmidt CM. MEK inhibition of pancreatic carcinoma cells by U0126 and its effect in combination with sulindac. Pancreas 2003; 27: 337-44
69. Schmidt CM, Wang Y, Wiesenauer C. Novel combination of cyclooxygenase-2 and MEK inhibitors in human hepatocellular carcinoma provides a synergistic increase in apoptosis. J Gastrointest Surg 2003; 7: 1024-33
70. Taxman DJ, MacKeigan JP, Clements C, et al. Transcriptional profiling of targets for combination therapy of lung carcinoma with paclitaxel and mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor. Cancer Res 2003; 63: 5095-104
71. Zelivianski S, Spellman M, Kellerman M, et al. ERK inhibitor PD98059 enhances docetaxel-induced apoptosis of androgen-independent human prostate cancer cells. Int J Cancer 2003; 107: 478-85
72. Morgan MA, Dolp O, Reuter CW. Cell-cycle-dependent activation of mitogen-activated protein kinase kinase (MEK-1/2) in myeloid leukemia cell lines and induction of growth inhibition and apoptosis by inhibitors of RAS signaling. Blood 2001; 97: 1823-34
73. Boucher MJ, Morisset J, Vachon PH, et al. MEK/ERK signaling pathway regulates the expression of Bcl-2, Bcl-X(L), and Mcl-1 and promotes survival of human pancreatic cancer cells. J Cell Biochem 2000; 79: 355-69
74. Horiuchi KY, Scherle PA, Trzaskos JM, et al. Competitive inhibition of MAP kinase activation by a peptide representing the alpha C helix of ERK. Biochemistry 1998; 37: 8879-85
75. Bianchini M, Radrizzani M, Brocardo MG, et al. Specific oligobodies against ERK-2 that recognize both the native and the denatured state of the protein. J Immunol Methods 2001; 252: 191-7
76. Fresno Vara JA, Casado E, de Castro J, et al. PI3K/Akt signalling pathway and cancer. Cancer Treat Rev 2004; 30: 193-204
77. Whitman M, Kaplan DR, Schaffhausen B, et al. Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation. Nature 1985; 315: 239-42
78. Whitman M, Downes CP, Keeler M, et al. Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate. Nature 1988; 332: 644-6
79. Pommier Y, Sordet O, Antony S, et al. Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks. Oncogene 2004; 23: 2934-49
80. Testa JR, Bellacosa A. AKT plays a central role in tumorigenesis. Proc Natl Acad Sci U S A 2001; 98: 10983-5
81. Hill MM, Hemmings BA. Inhibition of protein kinase B/Akt: implications for cancer therapy. Pharmacol Ther 2002; 93: 243-51
82. Scheid MP, Woodgett JR. Unravelling the activation mechanisms of protein kinase B/Akt. FEBS Lett 2003; 546: 108-12
83. Tsuruo T, Naito M, Tomida A, et al. Molecular targeting therapy of cancer: drug resistance, apoptosis and survival signal. Cancer Sci 2003; 94: 15-21
84. Maira SM, Galetic I, Brazil DP, et al. Carboxyl-terminal modulator protein (CTMP), a negative regulator of PKB/Akt and v-Akt at the plasma membrane. Science 2001; 294: 374-80
85. Obata T, Yaffe MB, Leparc GG, et al. Peptide and protein library screening defines optimal substrate motifs for AKT/PKB. J Biol Chem 2000; 275: 36108-15
86. Tsugawa K, Jones MK, Sugimachi K, et al. Biological role of phosphatase PTEN in cancer and tissue injury healing. Front Biosci 2002; 7: e245-51
87. Datta SR, Brunet A, Greenberg ME. Cellular survival: a play in three Akts. Genes Dev 1999; 13: 2905-27
88. Cardone MH, Roy N, Stennicke HR, et al. Regulation of cell death protease caspase-9 by phosphorylation. Science 1998; 282: 1318-21
89. Kops GJ, de Ruiter ND, De Vries-Smits AM, et al. Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature 1999 Apr 15; 398: 630-4
90. Pugazhenthi S, Nesterova A, Sable C, et al. Akt/protein kinase B up-regulates Bcl-2 expression through cAMP-response element-binding protein. J Biol Chem 2000; 275: 10761-6
91. Asnaghi L, Calastretti A, Bevilacqua A, et al. Bcl-2 phosphorylation and apoptosis activated by damaged microtubules require mTOR and are regulated by Akt. Oncogene 2004; 23: 5781-91
92. Lauder A, Castellanos A, Weston K. c-Myb transcription is activated by protein kinase B (PKB) following interleukin 2 stimulation of Tcells and is required for PKB-mediated protection from apoptosis. Mol Cell Biol 2001; 21: 5797-805
93. Blume-Jensen P, Hunter T. Oncogenic kinase signalling. Nature 2001; 411: 355-65
94. Wang GL, Iakova P, Wilde M, et al. Liver tumors escape negative control of proliferation via PI3K/Akt-mediated block of C/EBP alpha growth inhibitory activity. Genes Dev 2004; 18: 912-25
95. Jiang K, Sun J, Cheng J, et al. Akt mediates Ras downregulation of RhoB, a suppressor of transformation, invasion, and metastasis. Mol Cell Biol 2004; 24: 5565-76
96. Elstrom RL, Bauer DE, Buzzai M, et al. Akt stimulates aerobic glycolysis in cancer cells. Cancer Res 2004; 64: 3892-9
97. Carraway H, Hidalgo M. New targets for therapy in breast cancer: mammalian target of rapamycin (mTOR) antagonists. Breast Cancer Res 2004; 6: 219-24
98. Panwalkar A, Verstovsek S, Giles FJ. Mammalian target of rapamycin inhibition as therapy for hematologic malignancies. Cancer 2004; 100: 657-66
99. Chang F, Lee JT, Navolanic PM, et al. Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy. Leukemia 2003; 17: 590-603
100. Zhang G, He B, Weber GF. Growth factor signaling induces metastasis genes in transformed cells: molecular connection between Akt kinase and osteopontin in breast cancer. Mol Cell Biol 2003; 23: 6507-19
101. Edwards J, Krishna NS, Witton CJ, et al. Gene Amplifications associated with the development of hormone-resistant prostate cancer. Clin Cancer Res 2003; 9: 5271-81
102. Knuefermann C, Lu Y, Liu B, et al. HER2/PI-3K/Akt activation leads to a multidrug resistance in human breast adenocarcinoma cells. Oncogene 2003; 22: 3205-12
103. Gupta AK, Cerniglia GJ, Mick R, et al. Radiation sensitization of human cancer cells in vivo by inhibiting the activity of PI3K using LY294002. Int J Radiat Oncol Biol Phys 2003; 56: 846-53
104. Terakawa N, Kanamori Y, Yoshida S. Loss of PTEN expression followed by Akt phosphorylation is a poor prognostic factor for patients with endometrial cancer. Endocr Relat Cancer 2003; 10: 203-8
105. Bedogni B, O'Neill MS, Welford SM, et al. Topical treatment with inhibitors of the phosphatidylinositol 3′-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways reduces melanoma development in severe combined immunodeficient mice. Cancer Res 2004; 64: 2552-60
106. Wendel HG, De Stanchina E, Fridman JS, et al. Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy. Nature 2004; 428: 332-7
107. Martelli AM, Tazzari PL, Tabellini G, et al. A new selective AKT pharmacological inhibitor reduces resistance to chemotherapeutic drugs, TRAIL, all-trans-retinoic acid, and ionizing radiation of human leukemia cells. Leukemia 2003; 17: 1794-805
108. Castillo SS, Brognard J, Petukhov PA, et al. Preferential inhibition of Akt and killing of Akt-dependent cancer cells by rationally designed phosphatidylinositol ether lipid analogues. Cancer Res 2004; 64: 2782-92
109. Yang L, Dan HC, Sun M, et al. Akt/protein kinase B signaling inhibitor-2, a selective small molecule inhibitor of Akt signaling with antitumor activity in cancer cells overexpressing Akt. Cancer Res 2004; 64: 4394-9
110. Saito Y, Swanson X, Mhashilkar AM, et al. Adenovirus-mediated transfer of the PTEN gene inhibits human colorectal cancer growth in vitro and in vivo. Gene Ther 2003; 10: 1961-9
111. Liu X, Shi Y, Han EK, et al. Downregulation of Akt1 inhibits anchorage-independent cell growth and induces apoptosis in cancer cells. Neoplasia 2001; 3: 278-86
112. Sansal I, Sellers WR. The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol 2004; 22: 2954-63
113. Atkins MB, Hidalgo M, Stadler WM, et al. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol 2004; 22: 909-18
114. Beebe SJ, Corbin JD. Cyclic nucleotide-dependent protein kinases. In: Boyer PD, Kerbes EG, editors. The enzymes: control by phosphorylation. New York: Academic Press, 1986; 17: 43-111
115. Cho-Chung YS, Pepe S, Clair T, et al. cAMP-dependent protein kinase: role in normal and malignant growth. Crit Rev Oncol Hematol 1995; 21: 33-61
116. Cho-Chung YS, Clair T. The regulatory subunit of cAMP-dependent protein kinase as a target for chemotherapy of cancer and other cellular dysfunctional related diseases. Pharmacol Ther 1993; 60: 265-88
117. Bossis I, Voutetakis A, Bei T, et al. Protein kinase A and its role in human neoplasia: the Carney complex paradigm. Endocr Relat Cancer 2004; 11: 265-80
118. Young MR, Montpetit M, Lozano Y, et al. Regulation of Lewis lung carcinoma invasion and metastasis by protein kinase A. Int J Cancer 1995; 61: 104-9
119. Miller WR, Hulme MJ, Bartlett JM, et al. Changes in messenger RNA expression of protein kinase A regulatory subunit Iα in breast cancer patients treated with tamoxifen. Clin Cancer Res 1997; 3: 2399-404
120. McDaid HM, Cairns MT, Atkinson RJ, et al. Increased expression of the RIα subunit of the cAMP-dependent protein kinase A is associated with advanced stage ovarian cancer. Br J Cancer 1999; 79: 933-9
121. Bradbury AW, Carter DC, Miller WR, et al. Protein kinase A (PK-A) regulatory subunit expression in colorectal cancer and related mucosa. Br J Cancer 1994; 69: 738-42
122. Cho YS, Park YG, Lee YN, et al. Extracellular protein kinase A as a cancer biomarker: its expression by tumor cells and reversal by a myristate-lacking Cα and RIIβ subunit overexpression. Proc Natl Acad Sci U S A 2000; 97: 835-40
123. Rohlff C, Glazer R. Regulation of multidrug resistance through the cAMP and EGF signalling pathways. Cell Signal 1995; 7: 431-4
124. Cvijic ME, Chin KV. Effects of RIα overexpression on cisplatin sensitivity in human ovarian carcinoma cells. Biochem Biophys Res Commun 1998; 249: 723-7
125. Michalides R, Griekspoor A, Balkenende A, et al. Tamoxifen resistance by a conformational arrest of the estrogen receptor alpha after PKA activation in breast cancer. Cancer Cell 2004; 5: 597-605
126. Cho-Chung YS, Nesterova M, Pepe S, et al. Antisense DNA-targeting protein kinase A-RIα subunit: a novel approach to cancer treatment. Front Biosci 1999; 4: d859-68
127. Wang H, Cai Q, Zeng X, et al. Anti-tumor activity and pharmacokinetics of a mixed-backbone antisense oligonucleotide targeted to RIα subunit of protein kinase A after oral administration. Proc Natl Acad Sci U S A 1999; 96: 13989-94
128. Tortora G, Bianco R, Damiano V, et al. Oral antisense that targets protein kinase A cooperates with taxol and inhibits tumor growth, angiogenesis, and growth factor production. Clin Cancer Res 2000; 6: 2506-12
129. Nesterova MV, Cho-Chung YS. Antisense protein kinase A RIalpha inhibits 7,12-dimethylbenz(a)anthracene-induction of mammary cancer: blockade at the initial phase of carcinogenesis. Clin Cancer Res 2004; 10: 4568-77
130. Tortora G, Ciardiello F. Antisense targeting protein kinase A type I as a drug for integrated strategies of cancer therapy. Ann N Y Acad Sci 2003; 1002: 236-43
131. Cho YS, Kim MK, Cheadle C, et al. Antisense DNAs as multisite genomic modulators identified by DNA microarray. Proc Natl Acad Sci U S A 2001; 98: 9819-23
132. Chen HX, Marshall JL, Ness E, et al. A safety and pharmacokinetic study of a mixed-backbone oligonucleotide (GEM231) targeting the type I protein kinase A by two-hour infusion in patients with refractory solid tumors. Clin Cancer Res 2000; 6: 1259-66
133. Mani S, Goel S, Nesterova M, et al. Clinical studies in patients with solid tumors using a second-generation antisense oligonucleotide (GEM 231) targeted against protein kinase A type I. Ann N Y Acad Sci 2003; 1002: 252-62
134. Pekarsky Y, Hallas C, Croce CM. Molecular basis of mature T-cell leukemia. JAMA 2001; 286: 2308-14
135. Virgilio L, Narducci MG, Isobe M, et al. Identification of the TCL1 gene involved in T-cell malignancies. Proc Natl Acad Sci U S A 1994; 91: 12530-4
136. Petock JM, Torshin IY, Wang YF, et al. Structure of murine Tcl1 at 2.5 A resolution and implications for the TCL oncogene family. Acta Crystallogr D Biol Crystallogr 2001; 57: 1545-51
137. Yuille MR, Condie A, Stone EM, et al. TCL1 is activated by chromosomal rearrangement or by hypomethylation. Genes Chromosomes Cancer 2001; 30: 336-41
138. Gold MR. Akt is TCL-ish: implications for B-cell lymphoma. Trends Immunol 2003; 24: 104-8
139. Narducci MG, Fiorenza MT, Kang SM, et al. TCL1 participates in early embryonic development and is overexpressed in human seminomas. Proc Natl Acad Sci U S A 2002; 99: 11712-7
140. Pekarsky Y, Hallas C, Isobe M, et al. Abnormalities at 14q32.1 in T cell malignancies involve two oncogenes. Proc Natl Acad Sci U S A 1999; 96: 2949-51
141. Patrone L, Henson SE, Teodorovic J, et al. Gene expression patterns in AIDS versus non-AIDS-related diffuse large B-cell lymphoma. Exp Mol Pathol 2003; 74: 129-39
142. Lock RB. TCL1: a new drug target in lymphoid and germ-cell malignancies? Int J Biochem Cell Biol 2003; 35: 1614-8
143. Laine J, Kunstle G, Obata T, et al. Differential regulation of Akt kinase isoforms by the members of the TCL1 oncogene family. J Biol Chem 2002; 277: 3743-51
144. Scheid MP, Woodgett JR. PKB/AKT: functional insights from genetic models. Nat Rev Mol Cell Biol 2001; 2: 760-8
145. Kunstle G, Laine J, Pierron G, et al. Identification of Akt association and oligomerization domains of the Akt kinase coactivator TCL1. Mol Cell Biol 2002; 22: 1513-25
146. Laine J, Kunstle G, Obata T, et al. The protooncogene TCL1 is an Akt kinase coactivator. Mol Cell 2000; 6: 395-407
147. Pekarsky Y, Koval A, Hallas C, et al. Tcl1 enhances Akt kinase activity and mediates its nuclear translocation. Proc Natl Acad Sci U S A 2000; 97: 3028-33
148. Hoyer KK, French SW, Turner DE, et al. Dysregulated TCL1 promotes multiple classes of mature B cell lymphoma. Proc Natl Acad Sci U S A 2002; 99: 14392-7