Altered Expression of the Cell Cycle Regulatory Molecules pRb, p53 and MDM2 Exert a Synergetic Effect on Tumor Growth and Chromosomal Instability in Non-small Cell Lung Carcinomas (NSCLCs)

Molecular Medicine

Volumn 6, Issue 3, 2000, Pages 208-237

  Gorgoulis, V G ^a,b   Zacharatos, P ^a,b   Kotsinas, A ^a,b   Mariatos, G ^a   Liloglou, T ^b   Vogiatzi, T ^a   Foukas, P ^a   Rassidakis, G ^a   Garinis, G ^a   Ioannides, T ^a   Zoumpourlis, V ^a   Bramis, J ^c   Michail, P O ^c   Asimacopoulos, P J ^a   Field, J K ^b   Kittas, Ch ^a  

^a UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

^b Roy Castle   (United Kingdom)

^c UNIVERSITY OF ATHENS   (Greece)

Author keywords

Cell Cycle Regulatory Molecules; EACH ELEMENT; MDM2 mRNA; Ploidy Status; RELATIONSHIP WITH

Indexed keywords

MDM2 PROTEIN, HUMAN; MESSENGER RNA; NUCLEAR PROTEIN; ONCOPROTEIN; PRIMER DNA; PROTEIN MDM2; PROTEIN P53; RETINOBLASTOMA PROTEIN; RNA;

ALLELE; ANEUPLOIDY; APOPTOSIS; ARTICLE; BIOLOGICAL MODEL; CELL CULTURE; CELL DIVISION; DIPLOIDY; GENE EXPRESSION; GENETICS; HUMAN; LUNG NON SMALL CELL CANCER; LUNG TUMOR; METABOLISM; NUCLEOTIDE SEQUENCE; PATHOLOGY; TUMOR SUPPRESSOR GENE;

ALLELES; ANEUPLOIDY; APOPTOSIS; BASE SEQUENCE; CARCINOMA, NON-SMALL-CELL LUNG; CELL DIVISION; DIPLOIDY; DNA PRIMERS; GENE EXPRESSION; GENES, P53; GENES, RETINOBLASTOMA; HUMANS; LUNG NEOPLASMS; MODELS, BIOLOGICAL; NUCLEAR PROTEINS; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-MDM2; RETINOBLASTOMA PROTEIN; RNA, MESSENGER; RNA, NEOPLASM; TUMOR CELLS, CULTURED; TUMOR SUPPRESSOR PROTEIN P53;

MLCS; MLOWN;

EID: 0034149995     PISSN: 10761551     EISSN: 15283658     Source Type: Journal    
DOI: 10.1007/BF03402115     Document Type: Review

References (111)

1. A.G. Pauvlovich D.P. Toczyski L.H. Hartwell When checkpoints fail Cell 1997 88 315 321 10.1016/S0092-8674(00)81870-X
2. M. Serrano A.W. Lin M.E. McCurrach D. Beach S.W. Lowe Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a Cell 1997 88 593 602 9054499 10.1016/S0092-8674(00)81902-9 1:CAS:528:DyaK2sXhvVSit7k%3D
3. M.S. Greenblatt W.P. Bennett M. Hollstein C.C. Harris Mutations in the p53 tumour suppressor gene: Clues to cancer etiology and molecular pathogenesis Cancer Res. 1995 54 4855 4878
4. G. Mulligan T. Jacks The retinoblastoma gene family: cousins with overlapping interests Trends Genet. 1998 14 223 229 9635405 10.1016/S0168-9525(98)01470-X 1:CAS:528:DyaK1cXjslantLY%3D
5. X. Grana J. Garigga X. Mayol Role of retinoblastoma protein family, pRB, p107 and p130 in the negative control of cell growth Oncogene 1998 17 3365 3383 9916999 10.1038/sj.onc.1202575
6. N. Dyson The regulation of E2F by pRB-family proteins Genes Dev. 1998 12 2245 2262 9694791 10.1101/gad.12.15.2245 1:CAS:528:DyaK1cXltlagu74%3D
7. M. Hengstschlager K. Braun T. Soucek A. Miloloza E. Hengstschlager-Ottnad Cyclin-dependent kinases at the G1-S transition of the mammalian cell cycle Mutat. Res. 1999 436 1 9 9878675 10.1016/S1383-5742(98)00022-2 1:CAS:528:DyaK1cXotFWhurs%3D
8. D.A. Haas Kogan S.C. Kogan D. Levi et al. Inhibition of apoptosis by the retinoblastoma gene product EMBO J. 1995 14 461 472 7859736 398104 10.1002/j.1460-2075.1995.tb07022.x 1:CAS:528:DyaK2MXjs1KgsbY%3D
9. C. Prives P.A. Hall The p53 pathway J. Pathol. 1999 187 112 126 10341712 10.1002/(SICI)1096-9896(199901)187:1<112::AID-PATH250>3.0.CO;2-3 1:CAS:528:DyaK1MXmvVKrtQ%3D%3D
10. Y. Haupt R. Maya A. Kazaz M. Oren Mdm2 promotes the rapid degradation of p53 Nature 1997 387 296 299 9153395 10.1038/387296a0 1:CAS:528:DyaK2sXjtlSgtL8%3D
11. M.H. Kubbutat S.N. Jones K.H. Voysden Regulation of p53 stability by mdm2 Nature 1997 387 299 303 9153396 10.1038/387299a0 1:CAS:528:DyaK2sXjtlSgtLc%3D
12. Z.X. Xiao J. Chen A.J. Levine et al. Interaction between the retinoblastoma protein and the oncoprotein MDM2 Nature 1995 375 694 698 7791904 10.1038/375694a0 1:CAS:528:DyaK2MXmsFKrt7k%3D
13. J.-K. Hsieh F.S.G. Chan D.J. O’Connor S. Mittnacht S. Zhong X. Lu Rb regulates the stability and the apoptotic function of p53 via MDM2 Mol. Cell. 1999 3 181 193 10078201 10.1016/S1097-2765(00)80309-3 1:CAS:528:DyaK1MXhs12rsbo%3D
14. J. Piette H. Neel V. Marechal Mdm2: keeping p53 under control Oncogene 1997 15 1001 1010 9285554 10.1038/sj.onc.1201432 1:CAS:528:DyaK2sXmtVKisrw%3D
15. T. Juven-Gershon M. Oren Mdm2: The Ups and Downs Mol. Med. 1999 5 71 83 10203572 2230410 1:CAS:528:DyaK1MXjsF2mtb4%3D 10.1007/BF03402141
16. D.C. Olson V. Marechal J. Momand J. Chen C. Romocki A.J. Levine Identification and characterization of multiple mdm-2 proteins and mdm-2-p53 protein complexes Oncogene 1993 8 2353 2360 7689721 1:CAS:528:DyaK3sXms1Okt78%3D
17. I. Sigalas A.H. Calvert J.J. Anderson D.E. Neal J. Lunec Alternatively spliced mdm2 transcripts with loss of p53 binding domain sequences: transforming ability and frequent detection in human cancer Nat. Med. 1996 8 912 917 10.1038/nm0896-912
18. C. Cordon-Cardo E. Latres M. Drobnjak et al. Molecular abnormalities of mdm2 and p53 genes in adult soft tissue sarcomas Cancer Res. 1994 54 794 799 8306343 1:CAS:528:DyaK2cXhs1Sgsb4%3D
19. G. Reifenberger L. Liu K. Ichimura E.E. Schmidt V.P. Collins Amplification and overexpression of the MDM2 gene in a subset of human gliomas without p53 mutations Cancer Res. 1993 58 2736 2739
20. J.M. Gudas H. Nguyen R.C. Kelin D. Katayose P. Seth K.H. Cowan Differential expression of multiple MDM2 messenger RNAs and proteins in normal and tumorigenic epithelial breast cells Clin. Cancer Res. 1995 1 71 80 9815889 1:CAS:528:DyaK2MXlvVarsr0%3D
21. P. Lianes I. Orlow Z.F. Zhang et al. Altered patterns of MDM2 and TP53 expression in human bladder cancer J. Natl. Cancer Inst. 1994 86 1325 1330 8064890 10.1093/jnci/86.17.1325 1:CAS:528:DyaK2cXmsFaksbw%3D
22. V.G. Gorgoulis G.Z. Rassidakis A.M. Karameris et al. Immunohistochemical and molecular evaluation of the mdm-2 gene product in bronchogenic carcinoma Mod. Pathol. 1996 9 544 554 8733770 1:STN:280:DyaK28zhsFOrug%3D%3D
23. V.G. Gorgoulis V. Zoumpourlis G.Z. Rassidakis et al. A molecular and immunohistochemical study of the MDM2 protein isoforms and p53 gene product in bronchogenic carcinoma J. Pathol. 1996 180 129 137 8976869 10.1002/(SICI)1096-9896(199610)180:2<129::AID-PATH646>3.0.CO;2-8 1:CAS:528:DyaK28XntFClt7c%3D
24. V.G. Gorgoulis P. Zacharatos A. Kotsinas et al. Alterations of the p16-pRb pathway and the chromosome locus 9p21-22 in non-small-cell lung carcinomas: relationship with p53 and MDM2 protein expression Am. J. Pathol. 1998 153 1749 1765 9846966 2233978 10.1016/S0002-9440(10)65690-8 1:CAS:528:DyaK1cXotV2ku7w%3D
25. M. Higashiyama O. Doi K. Kodama et al. MDM2 gene amplification and expression in non-small-cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation Br. J. Cancer 1997 75 1302 1308 9155050 2228229 10.1038/bjc.1997.221 1:STN:280:DyaK2s3pvF2jsw%3D%3D
26. D.S. Haines The mdm2 proto-oncogene Leuk. Lymphoma 1997 26 227 238 9322885 10.3109/10428199709051772 1:CAS:528:DyaK1cXnsFGktb4%3D
27. D.R. Brown C.A. Thomas S.P. Deb The human oncoprotein MDM2 arrests the cell cycle: elimination of its cell-cycle-inhibitory function induces tumorigenesis EMBO J. 1998 9 2513 2525 10.1093/emboj/17.9.2513
28. C. Lengauer K.W. Kinzler B. Vogelstein Genetic instabilities in human cancers Nature 1998 396 643 649 9872311 10.1038/25292 1:CAS:528:DyaK1MXisVWqsQ%3D%3D
29. S.J. Elledge Cell cycle checkpoints: preventing an identity crisis Science 1996 274 1664 1672 8939848 10.1126/science.274.5293.1664 1:CAS:528:DyaK28XntlyktL0%3D
30. L.S. Agapova G.V. Ilyinskaya N.A. Turovets et al. Chromosome changes caused by alterations of p53 expression Mutat. Res. 1996 354 129 138 8692199 10.1016/0027-5107(96)00062-0
31. T. Waldman C. Lengauer K.W. Kinzler B. Vogelstein Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking p21 Nature 1996 381 713 716 8649519 10.1038/381713a0 1:CAS:528:DyaK28XjslGmtbc%3D
32. A. Gualberto K. Aldape K. Kozakiewicz T.D. Tlsty An oncogenic form of p53 confers a dominant, gain-of-function phenotype that disrupts spindle checkpoint control. Proc Natl. Acad. Sci. U.S.A. 1998 95 5166 5171 10.1073/pnas.95.9.5166 1:CAS:528:DyaK1cXivV2jsbc%3D
33. M.B. Kastan O. Onyekwere D. Sidransky B. Vogelstein R.W. Craig Participation of p53 protein in the cellular response to DNA damage Cancer Res. 1991 51 6304 6311 1933891 1:CAS:528:DyaK38XhvFSltg%3D%3D
34. R.S. Paules E.N. Levedakou S.J. Wilson et al. Defective G2 checkpoint function in cells from individuals with familial cancer syndromes Cancer Res. 1995 55 1763 1773 7712486 1:CAS:528:DyaK2MXltVSlsLY%3D
35. S. Martin D. Green Apoptosis and cancer: the failure of controls on cell death and cell survival Crit. Rec. Oncol. Hematol. 1995 18 137 153 10.1016/1040-8428(94)00124-C 1:STN:280:DyaK2M3gvFOluw%3D%3D
36. E.A. Harrington J.L. Bruce E. Harlow N. Dyson pRB plays an essential role in cell cycle arrest induced by DNA damage Proc. Natl. Acad. Sci. U.S.A. 1998 95 11945 11950 9751770 21745 10.1073/pnas.95.20.11945 1:CAS:528:DyaK1cXmsV2htr0%3D
37. World Health Organization The World Health Organization histologic typing of lung tumours Am. J. Clin. Pathol. 1982 77 123 136 10.1093/ajcp/77.2.123
38. INK4a expression in resected non-small cell lung tumors Cancer Res. 1996 56 3415 3420 8758904 1:CAS:528:DyaK28Xks1els7w%3D
39. L.G. Davis M.D. Dibner J.F. Battey Basic Methods in Molecular Biology 1986 New York, NY Elsevier Science Publishing Co, Inc.
40. T. Liloglou P. Maloney G. Xinarianos S. Fear J.K. Field Sensitivity and limitations of high throughout fluorescent microsatellite analysis for the detection of allelic imbalance. Application in lung tumours Int. J. Oncol. 2000 16 5 14 10601542 1:CAS:528:DC%2BD3cXjvFWgsA%3D%3D
41. C.E. Bueso-Ramos Y. Yang E. deLeon P. McCown S.A. Stass M. Albitar The human MDM-2 oncogene is overexpressed in leukemias Blood 1993 82 2617 2623 8219216 1:CAS:528:DyaK2cXltFelsA%3D%3D
42. D.A. Freedman A.J. Levine Nuclear export is required for degradation of endogenous p53 by MDM2 and human papillomavirus E6 Mol. Cell Biol. 1998 18 7288 7293 9819415 109310 10.1128/MCB.18.12.7288 1:CAS:528:DyaK1cXnvVKlurk%3D
43. Y. Gavrieli Y. Serman S. Ben Sasson Identification of programmed cell death in situ via specific labelling of nuclear DNA fragmentation J. Cell Biol. 1992 119 493 501 1400587 10.1083/jcb.119.3.493 1:CAS:528:DyaK38XmtVyhsbs%3D
44. G.U. Auer U.G. Falkmer A.D. Zetterberg J.P.A. Baak Image cytometric nuclear DNA analysis in clinical tumor material Kapitel 15 I Manual of quantitative pathology in cancer diagnosis and prognosis 1991 Heidelberg, Germany. pp. Springer 211 232
45. T. Hirano B. Franzen H. Kato Y. Ebihara G. Auer Genesis of squamous cell lung carcinoma. Sequential changes of proliferation, DNA ploidy, and p53 expression Am. J. Pathol. 1994 144 296 302 7906095 1887133 1:STN:280:DyaK2c7ksVKkuw%3D%3D
46. T. Kawai M. Suzuki S. Kono et al. Proliferating cell nuclear antigen and Ki-67 in lung carcinoma: correlation with DNA flow cytometric analysis Cancer 1994 74 2468 2475 7923002 10.1002/1097-0142(19941101)74:9<2468::AID-CNCR2820740913>3.0.CO;2-X 1:STN:280:DyaK2M%2Fgslertw%3D%3D
47. D.C. Brown K.C. Gatter Monoclonal antibody Ki-67: its use in histopathology Histopathology 1990 17 489 503 2076881 10.1111/j.1365-2559.1990.tb00788.x 1:STN:280:DyaK3M7mvFCgsA%3D%3D (review)
48. Y. Sekido K.M. Fong J.D. Minna Progress in understanding the molecular pathogenesis of human lung cancer Biochim. Biophys. Acta. 1998 1378 F21 F59 9739759 1:CAS:528:DyaK1cXkvFOnurc%3D
49. H. Tanaka Y. Fujii H. Hirabayashi S. Miyoshi M. Sakaguchi H.E. Yoon H. Matsuda Disruption of the RB pathway and cell-proliferative activity in non-small cell lung cancers Int. J. Cancer (Pred. Oncol.) 1998 79 111 115 10.1002/(SICI)1097-0215(19980417)79:2<111::AID-IJC2>3.0.CO;2-W 1:CAS:528:DyaK1MXksl2ktbc%3D
50. A. Marchetti F. Buttitta S. Pellegrini et al. mdm2 gene amplification and overexpression in non-small cell lung carcinoma with accumulation of the p53 protein in the absence of p53 gene mutation Diagn. Mol. Pathol. 1995 4 93 97 7551299 10.1097/00019606-199506000-00004 1:STN:280:DyaK28%2FltlCrsw%3D%3D
51. A.G. Knudson Jr Mutation and cancer: statistical study of retinoblastoma Proc. Natl. Acad. Sci. U.S.A. 1971 68 820 823 5279523 389051 10.1073/pnas.68.4.820
52. J.E. Landers S.L. Cassel D.L. George Translational enhancement of mdm2 oncogene expression in human tumor cells containing a stabilized wild-type p53 protein Cancer Res. 1997 57 3562 3568 9270029 1:CAS:528:DyaK2sXls1Sgsrg%3D
53. Arf, interacts with MDM2 and neutralizes MDM2’s inhibition of p53 Cell 1998 92 713 723 9529248 10.1016/S0092-8674(00)81400-2 1:CAS:528:DyaK1cXit1KlsL8%3D
54. Y. Zhanf Y. Xiong W.G. Yarbrough ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways Cell 1998 92 725 734 10.1016/S0092-8674(00)81401-4
55. P.T. Reissmann H. Koga R. Takahashi et al. Inactivation of the retinoblastoma susceptibility gene in non-small-cell lung cancer Oncogene 1993 8 1913 1919 8390038 1:CAS:528:DyaK3sXlsFOht74%3D
56. D.C. Betticher G.R.M. White S. Vonlanthen et al. G1 control gene status is frequently altered in resectable non-small cell lung cancer Int. J. Cancer 1997 74 556 562 9355981 10.1002/(SICI)1097-0215(19971021)74:5<556::AID-IJC14>3.0.CO;2-4 1:CAS:528:DyaK2sXmvFCrs7o%3D
57. A. Borg Q.X. Zhang P. Alm H. Olsson G. Sellberg The retinoblastoma gene in breast cancer: allele loss is not correlated with loss of gene protein expression Cancer Res. 1992 52 2991 2994 1581913 1:CAS:528:DyaK38XktVGhtr0%3D
58. J. Ishikawa H.-J. Xu S.-X. Hu et al. Inactivation of the retinoblastoma gene in human bladder and renal cell carcinomas Cancer Res. 1991 51 5736 5743 1913692 1:CAS:528:DyaK3MXmsFeju7o%3D
59. S. Venkatachalam Y.P. Shi S.N. Jones et al. Retention of wild-type p53 in tumors from p53 heterozygous mice: reduction of p53 dosage can promote cancer formation EMBO J. 1998 17 4657 4667 9707425 1170795 10.1093/emboj/17.16.4657 1:CAS:528:DyaK1cXlslOhsLY%3D
60. D. Dittmer S. Pati G.P. Zambetti et al. Gain of function mutation in p53 Nat. Genet. 1993 4 42 46 8099841 10.1038/ng0593-42 1:CAS:528:DyaK3sXkt1ajsbo%3D
61. M. Hsiao J. Low E. Dorn et al. Gain-of-function mutations of the p53 gene induce lymphohematopoietic metastatic potential and tissue invasiveness Am. J. Pathol. 1994 145 702 714 8080050 1890319 1:CAS:528:DyaK2cXmslOksr8%3D
62. G. Blandino A.J. Levine M. Oren Mutant p53 gain of function: differential effects of different p53 mutants on resistance of cultured cells to chemotherapy Oncogene 1999 18 477 485 9927204 10.1038/sj.onc.1202314 1:CAS:528:DyaK1MXhtFOrsbY%3D
63. P.D. Smith S. Crossland G. Parker et al. Novel p53 mutants selected in BRCA2-associated tumours which dissociate transformation suppression from other wild-type p53 functions Oncogene 1999 18 2451 2459 10229196 10.1038/sj.onc.1202565 1:CAS:528:DyaK1MXjtV2murw%3D
64. S. Deb C.T. Jackson M.A. Subler D.W. Martin Modulation of cellular and viral promoters by mutant human p53 proteins found in tumor cells J. Virol. 1992 66 6164 6170 1356162 283665 1:CAS:528:DyaK38XmtV2qsbc%3D
65. P.K. Liu E. Kraus T.A. Wu L.C. Strong M.A. Tainsky Analysis of genomic instability in Li-Fraumeni fibroblasts with germline p53 mutations Oncogene 1996 12 2267 2278 8649766 2719722 1:CAS:528:DyaK28XjvFCmt7s%3D
66. H. Ishida K. Irie T. Itoh T. Furukawa O. Tokunaga The prognostic significance of p53 and bcl-2 expression in lung adenocarcinoma and its correlation with Ki-67 growth fraction Cancer 1997 80 1034 1045 9305703 10.1002/(SICI)1097-0142(19970915)80:6<1034::AID-CNCR5>3.0.CO;2-9 1:CAS:528:DyaK2sXmt1yis7s%3D
67. INK4 and retinoblastoma protein status in non-small cell lung cancer: Potential synergistic effect with altered p53 protein on proliferative activity Cancer Res. 1996 56 5557 5562 8971152 1:CAS:528:DyaK2sXis1Wk
68. D.H. Harpole Jr J.E. Herndon II W.G. Wolfe I.D. Iglehart J.R. Marks A prognostic model of recurrence and death in stage I non-small cell lung cancer utilizing presentation, histopathology, and oncoprotein expression Cancer Res. 1995 55 51 56 7805040 1:CAS:528:DyaK2MXivVGgu78%3D
69. O. Morkve O.J. Halvorsen L. Stangeland A. Gulsvik O.D. Laerum Quantitation of biological tumor markers (p53, c-myc, Ki-67 and DNA ploidy) by multiparameter flow cytometry in non-small-cell lung cancer Int. J. Cancer 1992 52 851 855 1334053 10.1002/ijc.2910520603 1:STN:280:DyaK3s%2FptlOrtQ%3D%3D
70. G. Fontanini D. Bigini S. Vignati et al. p53 expression in non small cell lung cancer: clinical and biological correlations Anticancer Res. 1993 13 737 742 8100413 1:STN:280:DyaK3szgsV2iug%3D%3D
71. A.J. O’Neill M.J. Staunton E.F. Gaffney Apoptosis occurs independently of bcl-2 and p53 over-expression in non-small cell lung carcinoma Histopathology 1996 29 45 50 8818693 10.1046/j.1365-2559.1996.d01-478.x
72. H.J. Xu P.T. Cagle S.X. Hu J. Li W.F. Benedict Altered retinoblastoma and p53 protein status in non-small cell carcinoma of the lung: potential synergistic effects on prognosis Clin. Cancer Res. 1996 2 1169 1176 9816284 1:STN:280:DyaK1M%2FjsFWgsA%3D%3D
73. H. Dosaka-Akita S.X. Hu M. Fujino et al. Altered retinoblastoma protein expression in nonsmall cell lung cancer: its synergistic effects with altered ras and p53 protein status on prognosis Cancer 1997 79 1329 1337 9083154 10.1002/(SICI)1097-0142(19970401)79:7<1329::AID-CNCR9>3.0.CO;2-B 1:STN:280:DyaK2s3js1Cmug%3D%3D
74. C. Cordon-Cardo Z.F. Zhang G. Dalbagni M. Drobnjak et al. Cooperative effects of p53 and pRB alterations in primary superficial bladder tumors Cancer Res. 1997 57 1217 1221 9102201 1:CAS:528:DyaK2sXit1Kqu74%3D
75. B.O. Williams L. Remington D.M. Albert S. Mukai R.T. Bronson T. Jacks Cooperative tumorigenic effects of germline mutations in Rb and p53 Nature Genet. 1994 7 480 484 7951317 10.1038/ng0894-480 1:CAS:528:DyaK2cXlsFCnsrY%3D
76. L. Yamasaki Balancing proliferation and apoptosis in vivo: the Goldilocks theory and E2F/DP action. Biochim Biophys. Acta 1999 1423 M9 M15 1:CAS:528:DyaK1MXhvVCnsbg%3D
77. H. Pan C. Yin N.J. Dyson E. Harlow L. Yamasaki T. Van Dyke Key roles for E2F1 in signaling p53-dependent apoptosis and in cell division within developing tumors Mol. Cell 1998 2 283 292 9774967 10.1016/S1097-2765(00)80273-7 1:CAS:528:DyaK1cXmsVyqt7k%3D
78. S. Bates A.C. Phillips P.A. Clark et al. P14ARF links the tumor suppressors RB and p53 Nature 1998 395 124 125 9744267 10.1038/25867 1:CAS:528:DyaK1cXmtVemsrY%3D
79. K. Martin D. Trouche C. Hagemeier Sorensen N.B. La Thangue T. Kouzarides Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoprotein Nature 1995 375 691 694 7791903 10.1038/375691a0 1:CAS:528:DyaK2MXmsFKrt7g%3D
80. R.P. Bissonnette F. Echeverri A. Mahboudi D.R. Green Apoptotic cell death induced by c-Myc is inhibited by bcl-2 Nature 1992 359 552 554 1406975 10.1038/359552a0 1:CAS:528:DyaK38XmtlWlsL0%3D
81. E.A. Harrington M.R. Bennett A. Fanidi G.I. Evan c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines EMBO J. 1994 13 3286 3295 8045259 395225 10.1002/j.1460-2075.1994.tb06630.x 1:CAS:528:DyaK2cXlt1Kjtbk%3D
82. K. Fukasawa G.F. Vande Woude Synergy between the Mos/Mitogen-Activated Protein Kinase pathway and loss of p53 function in transformation and chromosome instability Mol. Cell Biol. 1997 17 506 518 8972231 231775 10.1128/MCB.17.1.506 1:CAS:528:DyaK2sXhtlyrsQ%3D%3D
83. V.G. Gorgoulis P.V. Zacharatos E. Manolis et al. Effects of p53 mutants derived from lung carcinomas on the p53-responsive element (p53RE) of the MDM2 gene Br. J. Cancer 1998 77 374 384 9472631 2151306 10.1038/bjc.1998.60 1:CAS:528:DyaK1cXhtVylsLw%3D
84. T. Crook N.J. Marston E.A. Sara K.H. Vousden Trancriptional activation by p53 correlates with suppression of growth but not transformation Cell 1994 265 1582 1584
85. P.V. Zacharatos V.G. Gorgoulis A. Kotsinas et al. Modulation of wild-type p53 activity by mutant p53 R273H depends on the p53 responsive element (p53RE). A comparative study between the p53REs of the MDM2, WAF/Cip1 and Bax genes in the lung cancer environment Anticancer Res. 1999 19 579 588 10226602 1:CAS:528:DyaK1MXivFyis70%3D
86. E. Shaulian D. Resnitzky O. Shifman et al. Induction of Mdm2 and enhancement of cell survival by bFGF Oncogene 1997 15 2717 2725 9400998 10.1038/sj.onc.1201453 1:CAS:528:DyaK2sXotVWnsLk%3D
87. M. Volm R. Koomagi J. Mattern G. Stammler Prognostic value of basic fibroblast growth factor and its receptor (FGFR-1) in patients with non-small cell lung carcinomas Eur. J. Cancer 1997 33 691 693 9274456 10.1016/S0959-8049(96)00411-X 1:STN:280:DyaK2svhvF2msg%3D%3D
88. C. Prives Signaling to p53: Breaking the MDM2-p53 circuit Cell 1998 95 5 8 9778240 10.1016/S0092-8674(00)81774-2 1:CAS:528:DyaK1cXmslWmu7k%3D
89. S.R. Grossman M. Perez A.L. Kung et al. p300/MDM2 complexes participate in MDM2-mediated p53 degradation Mol. Cell 1998 2 405 415 9809062 10.1016/S1097-2765(00)80140-9 1:CAS:528:DyaK1cXntFSksr0%3D
90. M. Muraoka M. Konishi R. Kikuchi-Yanoshit et al. p300 gene alteration in colorectal and gastric carcinomas Oncogene 1996 12 1565 1569 8622873 1:CAS:528:DyaK28Xis12ntLs%3D
91. T. Shlott S. Reimer A. Jahns et al. Point mutations and nucleotide insertions in the MDM2 zinc finger structure of human tumors J. Pathol. 1997 182 54 61 10.1002/(SICI)1096-9896(199705)182:1<54::AID-PATH815>3.0.CO;2-I
92. K. Fukasawa T. Choi R. Kurivama S. Rulong G.F. Vande Woude Abnormal centrosome amplification in the absence of p53 Science 1996 271 1744 1747 8596939 10.1126/science.271.5256.1744 1:CAS:528:DyaK28XhvVWmsb4%3D
93. M. Volm T. Efferth J. Mattern Oncoprotein (c-myc, c-erbB1, c-erbB2, c-fos) and suppressor gene product (p53) expression in squamous cell carcinomas of the lung. Clinical and biological correlations Anticancer Res. 1992 12 11 20 1348920 1:STN:280:DyaK383jtFGjsQ%3D%3D
94. O. Morkve O.J. Halvorsen R. Skjaerven L. Stangeland A. Gulsvik O.D. Laerum Prognostic significance of p53 protein expression and DNA ploidy in surgically treated non-small cell lung carcinomas Anticancer Res. 1993 13 571 578 8391242 1:STN:280:DyaK3szgsVyqsg%3D%3D
95. A. Costa R. Silvestrini C. Mochen et al. p53 expression, DNA ploidy and S-phase cell fraction in operable locally advanced non-small-cell lung cancer Br. J. Cancer 1996 73 914 919 8611406 2074267 10.1038/bjc.1996.163 1:STN:280:DyaK287pt1Wrtw%3D%3D
96. P. Dalquen Moch-H G. Feichter et al. DNA aneuploidy, S-phase fraction, nuclear p53 positivity, and survival in non-small-cell lung carcinoma Virchows Arch. 1997 431 173 179 9334838 10.1007/s004280050085 1:STN:280:DyaK2svnsFeitg%3D%3D
97. Y. Cho S. Gorina P.D. Jeffrey N.P. Pavletich Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations Science 1994 265 346 355 8023157 10.1126/science.8023157 1:CAS:528:DyaK2cXlslegs7k%3D
98. T.E. Creighton Proteins, Structures and Molecular Properties 1984 New York, NY WH Freeman 235
99. D.P. Cahill C. Lengauer J. Yu et al. Mutations of mitotic checkpoint genes in human cancers Nature 1998 392 300 303 9521327 10.1038/32688 1:CAS:528:DyaK1cXitFahsro%3D
100. H. Hermeking C. Lengauer K. Polyak et al. 14-3-3 sigma is a p53-regulated inhibitor of G2/M progression Mol. Cell 1997 1 3 11 9659898 10.1016/S1097-2765(00)80002-7 1:CAS:528:DyaK1cXlt1Gqtw%3D%3D
101. S.A. Mehdi J.E. Etzell N.B. Newman et al. Prognostic significance of Ki-67 immunostaining and symptoms in resected stage I and II non-small cell lung cancer Lung Cancer 1998 20 99 108 9711528 10.1016/S0169-5002(98)00027-0 1:STN:280:DyaK1cznslCjtQ%3D%3D
102. J.L. Pujol J. Simony G. Jolimoy et al. Hypodiploidy, Ki-67 growth fraction and prognosis of surgically resected lung cancers Br. J. Cancer 1996 74 964 970 8826867 2074737 10.1038/bjc.1996.466 1:STN:280:DyaK28visVentg%3D%3D
103. G.V. Scaglioti M. Micela L. Gubetta et al. Prognostic significance of Ki-67 labelling in resected non small cell cancer Eur. J. Cancer 1993 29A 363 365 10.1016/0959-8049(93)90387-U
104. M.F. Tungekar K.C. Gatter M.S. Dunhill D.Y. Mason Ki-67 immunostaining and survival in operable lung cancer Histopathology 1991 19 545 550 1664810 10.1111/j.1365-2559.1991.tb01503.x 1:STN:280:DyaK387lsFKjuw%3D%3D
105. P.V. Zimmerman G.A. Hawson M.H. Bint P.G. Parsons Ploidy as a prognostic determinant in surgically treated lung cancer Lancet 1987 2 530 533 2887832 10.1016/S0140-6736(87)92923-0 1:STN:280:DyaL2szhtl2ksA%3D%3D
106. M. Volm J. Mattern T. Muller P. Drings Flow cytometry of epidermoid lung carcinomas: relationship of ploidy and cell cycle phases to survival. A five-year follow up study Anticancer Res. 1988 8 105 112 3358625 1:STN:280:DyaL1c7pt1agsw%3D%3D
107. H. Isobe H. Miyamoto T. Shimizu et al. Prognostic and therapeutic significance of flow cytometric nuclear DNA content in non-small cell lung cancer Cancer 1990 65 1391 1395 2155055 10.1002/1097-0142(19900315)65:6<1391::AID-CNCR2820650624>3.0.CO;2-K 1:STN:280:DyaK3c7mslKjtw%3D%3D
108. H. Miyamoto M. Harada H. Isobe et al. Prognostic value of nuclear DNA content and expression of the ras oncogene product in lung cancer Cancer Res. 1991 51 6346 6350 1657384 1:STN:280:DyaK38%2FjsVOlug%3D%3D
109. J. Ogawa T. Tsurumi H. Inoue A. Shohtsu Relationship between tumor DNA ploidy and regional lymph node changes in lung cancer Cancer 1992 69 1688 1695 1551053 10.1002/1097-0142(19920401)69:7<1688::AID-CNCR2820690708>3.0.CO;2-2 1:STN:280:DyaK383gtVeitg%3D%3D
110. G. Fontanini R. Pingitore D. Bigini et al. Growth fraction in non-small lung cancer estimated by proliferating cell nuclear antigen and comparison with Ki-67 labeling and DNA flow cytometry data Am. J. Pathol. 1992 141 1285 1290 1361306 1886777 1:CAS:528:DyaK3sXhs1Kgs7w%3D
111. M. Redondo A. Concha R. Oldivela et al. Expression of HLA class I and II antigens in bronchogenic carcinomas: its relationship to cellular DNA content and clinicalpathological parameters Cancer Res. 1991 51 4948 4954 1654207 1:STN:280:DyaK3MzntFentw%3D%3D