A Novel Ras Antagonist Regulates Both Oncogenic Ras and the Tumor Suppressor p53 in Colon Cancer Cells

Molecular Medicine

Volumn 6, Issue 8, 2000, Pages 693-704

  Halaschek Wiener, Julius ^a   Wacheck, Volker ^a   Schlagbauer Wadl, Hermine ^a   Wolff, Klaus ^b   Kloog, Yoel ^c   Jansen, Burkhard ^a,b  

^a Department of Clinical Pharmacology   (Austria)

^b Division of General Dermatology   (Austria)

^c TEL AVIV UNIVERSITY   (Israel)

Author keywords

Colon Cancer Cells; Cyclin Cyclin dependent Kinases (CDK); FTS Treatment; Trans farnesylthiosalicylic Acid; Treatment resistant Malignancies

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; CDKN1A PROTEIN, HUMAN; CYCLIN DEPENDENT KINASE; CYCLIN DEPENDENT KINASE INHIBITOR 1A; CYCLINE; DRUG DERIVATIVE; FARNESOL; FARNESYLTHIOSALICYLIC ACID; PROTEIN P21; PROTEIN P53; SALICYLIC ACID DERIVATIVE;

ARTICLE; CELL CULTURE; CELL DIVISION; CELL SIZE; COLON TUMOR; DRUG ANTAGONISM; DRUG EFFECT; FLOW CYTOMETRY; GENE EXPRESSION REGULATION; GENETIC TRANSFECTION; GENETICS; HUMAN; METABOLISM; MUTATION; PATHOLOGY; UPREGULATION; WESTERN BLOTTING;

BLOTTING, WESTERN; CELL DIVISION; CELL SIZE; COLONIC NEOPLASMS; CYCLIN-DEPENDENT KINASE INHIBITOR P21; CYCLIN-DEPENDENT KINASES; CYCLINS; FARNESOL; FLOW CYTOMETRY; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MUTATION; OLIGONUCLEOTIDES, ANTISENSE; ONCOGENE PROTEIN P21(RAS); SALICYLIC ACIDS; TRANSFECTION; TUMOR CELLS, CULTURED; TUMOR SUPPRESSOR PROTEIN P53; UP-REGULATION;

MLCS; MLOWN;

EID: 0034252166     PISSN: 10761551     EISSN: 15283658     Source Type: Journal    
DOI: 10.1007/BF03402049     Document Type: Article

References (57)

1. C.C. Boring T.S. Squires T. Tong S. Montgomery Cancer statistics, 1994 CA. Cancer J. Clin. 1994 44 7 26 10.3322/canjclin.44.1.7 1:STN:280:DyaK2c7gvVygsA%3D%3D 8281473
2. J.L. Bos E.R. Fearon S.R. Hamilton et al. Prevalence of ras gene mutations in human colorectal cancers Nature 1987 327 293 297 10.1038/327293a0 1:CAS:528:DyaL2sXktlCht78%3D 3587348
3. J.M. Nigro S.J. Baker A.C. Preisinger et al. Mutations in the p53 gene occur in diverse human tumour types Nature 1989 342 705 708 10.1038/342705a0 1:CAS:528:DyaK3cXkvFyhug%3D%3D 2531845
4. S.J. Baker E.R. Fearon J.M. Nigro et al. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas Science 1989 244 217 221 10.1126/science.2649981 1:CAS:528:DyaL1MXit12gt74%3D 2649981
5. K. Forrester C. Almoguera K. Han W.E. Grizzle M. Perucho Detection of high incidence of K-ras oncogenes during human colon tumorigenesis Nature 1987 327 298 303 10.1038/327298a0 1:CAS:528:DyaL2sXktlCht7w%3D 2438556
6. I.S. Glarakis S. Savva D.A. Spandidos Activation of the ras genes in malignant and pre-malignant colorectal tumors Oncol. Rep. 1998 5 1451 1454 1:CAS:528:DyaK1cXntFSrt7c%3D 9769386
7. X.F. Sun H. Ekberg H. Zhang J.M. Carstensen B. Nordenskjold Overexpression of ras is an independent prognostic factor in colorectal adenocarcinoma APMIS 1998 106 657 664 10.1111/j.1699-0463.1998.tb01396.x 1:STN:280:DyaK1czptFKgug%3D%3D 9725799
8. E. Brambilla C. Brambilla p53 and lung cancer Pathol. Biol. (Paris) 1997 45 852 863 1:CAS:528:DyaK1cXitVGrtLk%3D
9. C.C. Harris 1995 Deichmann lecture—p53 tumor suppressor gene: at the crossroads of molecular carcinogenesis, molecular epidemiology and cancer risk assessment Toxicol. Lett. 1995 82–83 1 7 10.1016/0378-4274(95)03643-1 8597035
10. P.W. Hinds C.A. Finlay R.S. Quartin et al. Mutant p53 DNA clones from human colon carcinomas cooperate with ras in transforming primary rat cells: a comparison of the “hot spot” mutant phenotypes Cell Growth Differ. 1990 1 571 580 1:CAS:528:DyaK3MXmslant78%3D 2288874
11. S. Bosari G. Viale The clinical significance of p53 aberrations in human tumours Virchows Arch. 1995 427 229 241 10.1007/BF00203389 1:STN:280:DyaK28%2Fpslagug%3D%3D 7496591
12. G.P. Zambetti J. Bargonetti K. Walker C. Prives A.J. Levine Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element Genes Dev. 1992 6 1143 1152 10.1101/gad.6.7.1143 1:CAS:528:DyaK3sXisV2is7c%3D 1628822
13. S. Fields S.K. Jang Presence of a potent transcription activating sequence in the p53 protein Science 1990 249 1046 1049 10.1126/science.2144363 1:CAS:528:DyaK3cXls1Klt70%3D 2144363
14. L. Raycroft H.Y. Wu G. Lozano Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene Science 1990 249 1049 1051 10.1126/science.2144364 2144364 1:CAS:528:DyaK3cXls1Klt7o%3D 2935288
15. S.J. Ullrich C.W. Anderson W.E. Mercer E. Appella The p53 tumor suppressor protein, a modulator of cell proliferation J. Biol. Chem. 1992 267 15259 15262 1:CAS:528:DyaK38XlsVyiu70%3D 1639769
16. J.W. Harper G.R. Adami N. Wei K. Keyomarsi S.J. Elledge The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases Cell 1993 75 805 816 10.1016/0092-8674(93)90499-G 1:CAS:528:DyaK2cXhtVShsLk%3D 8242751
17. Y. Xiong G.J. Hannon H. Zhang D. Casso R. Kobayashi D. Beach p21 is a universal inhibitor of cyclin kinases Nature 1993 366 701 704 10.1038/366701a0 1:CAS:528:DyaK2cXhsFOhtbw%3D 8259214
18. S. Waga G.J. Hannon D. Beach B. Stillman The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA Nature 1994 369 574 578 10.1038/369574a0 1:CAS:528:DyaK2cXlsFWnsrc%3D 7911228
19. Y. Luo J. Hurwitz J. Massague Cell-cycle inhibition by independent CDK and PCNA binding domains in p21Cip1 Nature 1995 375 159 161 10.1038/375159a0 1:CAS:528:DyaK2MXls1WisrY%3D 7753174
20. W.S. el-Deiry T. Tokino V.E. Velculescu et al. WAF1, a potential mediator of p53 tumor suppression Cell 1993 75 817 825 10.1016/0092-8674(93)90500-P 1:CAS:528:DyaK2cXpslGguw%3D%3D 8242752
21. T. Waldman K.W. Kinzler B. Vogelstein p21 is necessary for the p53-mediated G1 arrest in human cancer cells Cancer Res. 1995 55 5187 5190 1:CAS:528:DyaK2MXpsVarurw%3D 7585571
22. S.J. Baker A.C. Preisinger J.M. Jessup et al. p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis Cancer Res. 1990 50 7717 7722 1:CAS:528:DyaK3MXhvVOnsQ%3D%3D 2253215
23. Y. Saintigny D. Rouillard B. Chaput T. Soussi B.S. Lopez Mutant p53 proteins stimulate spontaneous and radiation-induced intrachromosomal homologous recombination independently of the alteration of the transactivation activity and of the G1 checkpoint Oncogene 1999 18 3553 3563 10.1038/sj.onc.1202941 1:CAS:528:DyaK1MXktlCkt7c%3D 10380877
24. P. Chene E. Bechter Cellular characterisation of p53 mutants with a single missense mutation in the beta-strand 326–333 and correlation of their cellular activities with in vitro properties J. Mol. Biol. 1999 288 891 897 10.1006/jmbi.1999.2738 1:CAS:528:DyaK1MXjtVersbo%3D 10329187
25. N.R. Rodrigues A. Rowan M.E. Smith et al. p53 mutations in colorectal cancer Proc. Natl. Acad. Sci. U. S. A. 1990 87 7555 7559 10.1073/pnas.87.19.7555 1699228 1:CAS:528:DyaK3cXmtVKjsL0%3D 54786
26. W.C. Hahn C.M. Counter A.S. Lundberg R.L. Beijersbergen M.W. Brooks R.A. Weinberg Creation of human tumour cells with defined genetic elements Nature 1999 400 464 468 10.1038/22780 1:CAS:528:DyaK1MXltVGmtLc%3D 10440377
27. B. Weisz K. Giehl M. Gana-Weisz et al. A new functional Ras antagonist inhibits human pancreatic tumor growth in nude mice Oncogene 1999 18 2579 2588 10.1038/sj.onc.1202602 1:CAS:528:DyaK1MXjtVygtLw%3D 10353601
28. Z. Aharonson M. Gana-Weisz T. Varsano R. Haklai D. Marciano Y. Kloog Stringent structural requirements for anti-Ras activity of S-prenyl analogues Biochim. Biophys. Acta 1998 1406 40 50 10.1016/S0925-4439(97)00077-X 1:CAS:528:DyaK1cXhtlOjtLk%3D 9545527
29. R. Haklai M.G. Weisz G. Elad et al. Dislodgment and accelerated degradation of Ras Biochemistry 1998 37 1306 1314 10.1021/bi972032d 1:CAS:528:DyaK1cXjsVKnsw%3D%3D 9477957
30. M. Gana-Weisz R. Haklai D. Marciano Y. Egozi G. Ben-Baruch Y. Kloog The Ras antagonist S-farnesylthiosalicylic acid induces inhibition of MAPK activation Biochem. Biophys. Res. Commun. 1997 239 900 904 10.1006/bbrc.1997.7582 1:CAS:528:DyaK2sXnsVOhs7c%3D 9367867
31. D. Marciano G. Ben-Baruch M. Marom Y. Egozi R. Haklai Y. Kloog Farnesyl derivatives of rigid carboxylic acids-inhibitors of ras-dependent cell growth J. Med. Chem. 1995 38 1267 1272 10.1021/jm00008a004 1:CAS:528:DyaK2MXkvVWruro%3D 7731012
32. M. Marom R. Haklai G. Ben-Baruch D. Marciano Y. Egozi Y. Kloog Selective inhibition of Ras-dependent cell growth by farnesylthiosalisylic acid J. Biol. Chem. 1995 270 22263 22270 10.1074/jbc.270.38.22263 1:CAS:528:DyaK2MXot1GhsLY%3D 7673206
33. A. Leibovitz J.C. Stinson W.B. McCombs C.E. McCoy K.C. Mazur N.D. Mabry Classification of human colorectal adenocarcinoma cell lines Cancer Res. 1976 36 4562 4569 1:STN:280:DyaE2s%2Fms1yjsA%3D%3D 1000501
34. M. Perucho M. Goldfarb K. Shimizu C. Lama J. Fogh M. Wigler Human-tumor-derived cell lines contain common and different transforming genes Cell 1981 27 467 476 10.1016/0092-8674(81)90388-3 1:CAS:528:DyaL38Xms1KisQ%3D%3D 6101201
35. T. Finkel C.J. Der G.M. Cooper Activation of ras genes in human tumors does not affect localization, modification, or nucleotide binding properties of p21 Cell 1984 37 151 158 10.1016/0092-8674(84)90310-6 1:CAS:528:DyaL2cXkt1Wnsrk%3D 6609772
36. C.J. Der G.M. Cooper Altered gene products are associated with activation of cellular rasK genes in human lung and colon carcinomas Cell 1983 32 201 208 10.1016/0092-8674(83)90510-X 1:CAS:528:DyaL3sXoslWjtw%3D%3D 6825168
37. N.E. Kohl F.R. Wilson S.D. Mosser et al. Protein farnesyltransferase inhibitors block the growth of ras-dependent tumors in nude mice Proc. Natl. Acad. Sci. U. S. A. 1994 91 9141 9145 10.1073/pnas.91.19.9141 8090782 1:CAS:528:DyaK2cXlvFGhtb8%3D 44763
38. V. Manne N. Yan J.M. Carboni et al. Bisubstrate inhibitors of farnesyltransferase: a novel class of specific inhibitors of ras transformed cells Oncogene 1995 10 1763 1779 1:CAS:528:DyaK2MXls1artLk%3D 7753553
39. Y. Egozi B. Weisz M. Gana-Weisz G. Ben-Baruch Y. Kloog Growth inhibition of ras-dependent tumors in nude mice by a potent ras-dislodging antagonist Int. J. Cancer 1999 80 911 918 10.1002/(SICI)1097-0215(19990315)80:6<911::AID-IJC18>3.0.CO;2-4 1:CAS:528:DyaK1MXhvVGgtbo%3D 10074926
40. C.A. Rowell J.J. Kowalczyk M.D. Lewis A.M. Garcia Direct demonstration of geranylgeranylation and farnesylation of Ki-Ras in vivo J. Biol. Chem. 1997 272 14093 14097 10.1074/jbc.272.22.14093 1:CAS:528:DyaK2sXjsFOjtro%3D 9162034
41. D.B. Whyte P. Kirschmeier T.N. Hockenberry et al. K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors J. Biol. Chem. 1997 272 14459 14464 10.1074/jbc.272.22.14459 1:CAS:528:DyaK2sXjsFygs74%3D 9162087
42. I.S. Glarakis S. Savva D.A. Spandidos Activation of the ras genes in malignant and pre-malignant colorectal tumors Oncol. Rep. 1998 5 1451 1454 1:CAS:528:DyaK1cXntFSrt7c%3D 9769386
43. U. Kressner J. Bjorheim S. Westring et al. Ki-ras mutations and prognosis in colorectal cancer Eur. J. Cancer 1998 34 518 521 10.1016/S0959-8049(97)10111-3 1:CAS:528:DyaK1cXivFagsbw%3D 9713302
44. B. Jansen H. Schlagbauer-Wadl H. Kahr et al. Novel Ras antagonist blocks human melanoma growth Proc. Natl. Acad. Sci. U. S. A. 1999 96 14019 14024 10.1073/pnas.96.24.14019 10570191 1:CAS:528:DyaK1MXns1Oqu7w%3D 24183
45. T. Joneson M.A. White M.H. Wigler D. Bar-Sagi Stimulation of membrane ruffling and MAP kinase activation by distinct effectors of RAS Science 1996 271 810 812 10.1126/science.271.5250.810 1:CAS:528:DyaK28XptlyisA%3D%3D 8628998
46. M. Symons Rho family GTPases: the cytoskeleton and beyond Trends. Biochem. Sci. 1996 21 178 181 10.1016/S0968-0004(96)10022-0 1:CAS:528:DyaK28XivFenurw%3D 8871402
47. R. Seger N.G. Ahn T.G. Boulton et al. Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation Proc. Natl. Acad. Sci. U. S. A. 1991 88 6142 6146 10.1073/pnas.88.14.6142 1712480 1:CAS:528:DyaK38Xis1yj 52038
48. G.C. Prendergast J.P. Davide P.F. Lebowitz R. Wechsler-Reya N.E. Kohl Resistance of a variant ras-transformed cell line to phenotypic reversion by farnesyl transferase inhibitors Cancer Res. 1996 56 2626 2632 1:CAS:528:DyaK28XjtlCgu74%3D 8653708
49. G. Elad A. Paz R. Haklai D. Marciano A. Cox Y. Kloog Targeting of K-Ras 4B by S-trans,trans-farnesyl thiosalicylic acid Biochim. Biophys. Acta 1999 1452 228 242 10.1016/S0167-4889(99)00144-5 1:CAS:528:DyaK1MXnslyltrc%3D 10590312
50. N.M. Navone M.E. Labate P. Troncoso et al. p53 mutations in prostate cancer bone metastases suggest that selected p53 mutants in the primary site define foci with metastatic potential J. Urol. 1999 161 304 308 10.1016/S0022-5347(01)62136-0 1:CAS:528:DyaK1MXitFartw%3D%3D 10037428
51. C. Huang T. Taki M. Adachi T. Konishi M. Higashiyama M. Miyake Mutations in exon 7 and 8 of p53 as poor prognostic factors in patients with non-small cell lung cancer Oncogene 1998 16 2469 2477 10.1038/sj.onc.1201776 1:CAS:528:DyaK1cXjs12gt7o%3D 9627113
52. K. Ory Y. Legros C. Auguin T. Soussi Analysis of the most representative tumour-derived p53 mutants reveals that changes in protein conformation are not correlated with loss of transactivation or inhibition of cell proliferation EMBO J. 1994 13 3496 3504 395253 8062826 1:CAS:528:DyaK2cXlsFCntbc%3D 10.1002/j.1460-2075.1994.tb06656.x
53. B. Jansen E. Heere-Ress H. Schlagbauer-Wadl et al. Farnesylthiosalicylic acid inhibits the growth of human Merkel cell carcinoma in SCID mice J. Mol. Med. 1999 77 792 797 10.1007/s001099900052 1:CAS:528:DC%2BD3cXmsFSlsw%3D%3D 10619439
54. R. Li S. Waga G.J. Hannon D. Beach B. Stillman Differential effects by the p21 CDK inhibitor on PCNA-dependent DNA replication and repair Nature 1994 371 534 537 10.1038/371534a0 1:CAS:528:DyaK2cXmsV2lsLc%3D 7935768
55. M. Gorospe C. Cirielli X. Wang P. Seth M.C. Capogrossi N.J. Holbrook p21 (Waf1/Cip1) protects against p53-mediated apoptosis of human melanoma cells Oncogene 1997 14 929 935 10.1038/sj.onc.1200897 1:CAS:528:DyaK2sXhvFSlsLk%3D 9050992
56. W. Poluha D.K. Poluha B. Chang et al. The cyclin-dependent kinase inhibitor p21 (WAF1) is required for survival of differentiating neuroblastoma cells Mol. Cell Biol. 1996 16 1335 1341 10.1128/MCB.16.4.1335 8657106 1:CAS:528:DyaK28XhvVahtb0%3D 231117
57. L. Sepp-Lorenzino N. Rosen A farnesyl-protein transferase inhibitor induces p21 expression and G1 block in p53 wild type tumor cells J. Biol. Chem. 1998 273 20243 20251 10.1074/jbc.273.32.20243 1:CAS:528:DyaK1cXlsVWgt70%3D 9685373