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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1995 Jul;86(7):617–621. doi: 10.1111/j.1349-7006.1995.tb02442.x

Frequent Amplification of the Cyclin E Gene in Human Gastric Carcinomas

Yoshihiko Akama 1,2, Wataru Yasui 1, Hiroshi Yokozaki 1, Hiroki Kuniyasu 1, Kenji Kitahara 1, Takenori Ishikawa 2, Eiichi Tahara 1,✉
PMCID: PMC5920896  PMID: 7559076

Abstract

We searched for genetic alterations of the cyclin D1 and cyclin E genes in 45 human gastric carcinoma tissues. Expression of cyclin E mRNA and protein was also analyzed in eight of them by Northern and Western blots and immunohistochemical staining. The cyclin E gene was amplified 3–10 fold in seven gastric cancer tissues (15.6%), of which six were advanced gastric cancers. All of the cases with the cyclin E gene amplification displayed lymph node metastasis. Moreover, the case with the gene amplification overexpressed the cyclin E mRNA and protein. One of eight gastric cancer cell lines, MKN‐7, shared the cyclin E gene amplification, and all of the gastric cancer cell lines expressed high levels of the cyclin E mRNA and protein even without gene amplification. Amplification of the cyclin D1 gene was not observed in any of the gastric carcinoma tissues or gastric carcinoma cell lines. These results suggest that the gene amplification and overexpression of cyclin E play an important role in the abnormal growth and progression of gastric carcinoma.

Keywords: Cell cycle, G1 cyclins, G1/S transition

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REFERENCES

  • 1. ) Sherr , C. J.Mammalian G1 cyclins . Cell , 73 , 1059 – 1065 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Hunter , T. and Pines , J.Cyclins and cancer II: cyclin D and cdk inhibitors come of age . Cell , 79 , 573 – 582 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Xiong , Y. , Zhang , H. and Beach , D.D type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA . Cell , 71 , 505 – 514 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Dulić , V. , Lees , E. and Reed , S. I.Association of human cyclin E with a periodic G1‐S phase protein kinase . Science , 257 , 1958 – 1961 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Koff , A. , Giordano , A. , Desai , D. , Yamashita , K. , Harper , J. W. , Elledge , S. , Nishimoto , T. , Morgan , D. O. , Franza , B. R. and Roberts , J. M.Formation and activation of a cyclin E‐cdk2 complex during the G1 phase of the human cell cycle . Science , 257 , 1689 – 1694 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Motokura , T. , Bloom , T. , Kim , H. G. , Jüppner , H. , Ruderman , J. V. , Kronenberg , H. M. and Arnold , A.A novel cyclin encoded by a bcl1 ‐linked candidate oncogene . Nature , 350 , 512 – 515 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Tsuda , T. , Tahara , E. , Kajiyama , G. , Sakamoto , H. , Terada , M. and Sugimura , T.High incidence of coamplification of hst‐1 and int‐2 genes in human esophageal carcinomas . Cancer Res. , 49 , 5505 – 5508 ( 1989. ). [PubMed] [Google Scholar]
  • 8. ) Schuuring , E. , Verhoeven , E. , Mooi , W. J. and Michalides , R. J. A. M.Identification and cloning of two overexpressed genes, U21B31/PRAD1 and EMS1, within the amplified chromosome 11q13 region in human carcinomas . Oncogene , 7 , 355 – 361 ( 1992. ). [PubMed] [Google Scholar]
  • 9. ) Jiang , W. , Kahn , S. M. , Tomita , N. , Zhang , Y.‐J. , Lu , S.‐H. and Weinstein , I. B.Amplification of the human cyclin D gene in esophageal cancer . Cancer Res. , 52 , 2980 – 2983 ( 1992. ). [PubMed] [Google Scholar]
  • 10. ) Gillett , C. , Fantl , V. , Smith , R. , Fisher , C. , Bartek , J. , Dickson , C. , Barnes , D. and Peters , G.Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining . Cancer Res. , 54 , 1812 – 1817 ( 1994. ). [PubMed] [Google Scholar]
  • 11. ) Bukley , M. F. , Sweeny , K. J. E. , Hamilton , J. A.Sini , R. L. , Manning , D. L. , Nicholson , R. I. , deFazio , A. , Watts , C. K. W. , Musgrove , E. A. and Sutherland , R. L.Expression and amplification of cyclin genes in human breast cancer . Oncogene , 8 , 2127 – 2133 ( 1993. ). [PubMed] [Google Scholar]
  • 12. ) Nishida , N. , Fukuda , Y. , Komeda , T. , Kita , R. , Sando , T. , Furukawa , M. , Amenomori , M. , Shibagaki , I. , Nakao , K. , Ikenaga , M. and Ishizaki , K.Amplification and overexpression of the cyclin D1 gene in aggressive human hepatocellular carcinoma . Cancer Res. , 54 , 3107 – 3110 ( 1994. ). [PubMed] [Google Scholar]
  • 13. ) Keyomarsi , K. and Pardee , A. B.Redundant cyclin overexpression and gene amplification in breast cancer cells . Proc. Natl. Acad. Sci. USA , 90 , 1112 – 1116 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. ) Leach , F. S. , Elledge , S. J. , Sherr , C. J. , Willson , J. K. V. , Markowitz , S. , Kinzler , K. W. and Vogelstein , B.Amplification of cyclin genes in colorectal carcinomas . Cancer Res. , 53 , 1986 – 1989 ( 1993. ). [PubMed] [Google Scholar]
  • 15. ) Keyomarsi , K. , O'Leary , N. , Molnar , G. , Less , E. , Fingert , H. J. and Pardee , A. B.Cyclin E, a potential prognostic marker for breast cancer . Cancer Res. , 54 , 380 – 385 ( 1994. ). [PubMed] [Google Scholar]
  • 16. ) Sewing , A. , Ronicke , V. , Burger , C. , Funk , M. and Muller , R.Alternative splicing of human cyclin E . J. Cell Sci. , 107 , 581 – 588 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Ochiai , A. , Yasui , W. and Tahara , E.Growth‐promoting effect of gastrin on human gastric carcinoma cell line TMK‐1 . Jpn. J. Cancer Res. , 76 , 1064 – 1071 ( 1985. ). [PubMed] [Google Scholar]
  • 18. ) Yanagihara , K. , Seyama , T. , Tsumuraya , M. , Kamada , N. and Yokoro , K.Establishment and characterization of human signet ring cell gastric carcinoma cell lines with amplification of the c‐myc oncogene . Cancer Res. , 51 , 381 – 386 ( 1991. ). [PubMed] [Google Scholar]
  • 19. ) Yoshida , K. , Yokozaki , H. , Niimoto , M. , Ito , H. , Ito , M. and Tahara , E.Expression of TGF‐β and procollagen type I and type III in human gastric carcinomas . Int. J. Cancer , 44 , 394 – 398 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Lew , D. J. , Dulić , V. and Reed , S. I.Isolation of three human cyclins by rescue of G1 cyclin (cIn) function in yeast . Cell , 66 , 1197 – 1206 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Yasui , W. , Ayhan , A. , Kitadai , Y. , Nishimura , K. , Yokozaki , H. , Ito , H. and Tahara , E.Increased expression of p34cdc2 and its kinase activity in human gastric and colonic carcinomas . Int. J. Cancer , 53 , 36 – 41 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Yasui , W. , Ji , Z.‐Q. , Kuniyasu , H. , Ayhan , A. , Yokozaki , H. , Ito , H. and Tahara , E.Expression of transforming growth factor alpha in human tissues: immunohistochemical study and Northern blot analysis . Virchows Arch. A Pathol. Anat. , 421 , 513 – 519 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Hattori , Y. , Odagiri , H. , Nakatani , H. , Miyagawa , K. , Naito , K. , Sakamoto , H. , Katoh , O. , Yoshida , T. , Sugimura , T. and Terada , M.K‐sam, an amplified gene in stomach cancer, is a member of the heparin‐binding growth factor receptor genes . Proc. Natl. Acad. Sci. USA , 87 , 5983 – 5987 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. ) Kameda , T. , Yasui , W. , Yoshida , K. , Tsujino , T. , Nakayama , H. , Ito , M. , Ito , H. and Tahara , E.Expression of ERBB2 in human gastric carcinomas: relationship between p185ERBB2 expression and the gene amplification . Cancer Res. , 50 , 8002 – 8009 ( 1990. ). [PubMed] [Google Scholar]
  • 25. ) Kuniyasu , H. , Yasui , W. , Kitadai , Y. , Yokozaki , H. , Ito , H. and Tahara , E.Frequent amplification of the c‐met gene in scirrhous type stomach cancer . Biochem. Biophys. Res. Commun. , 189 , 227 – 232 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Nakatani , H. , Sakamoto , H. , Yoshida , T. , Yokota , J. , Tahara , E. , Sugimura , T. and Terada , M.Isolation of an amplified DNA sequence in stomach cancer . Jpn. J. Cancer Res. , 81 , 707 – 710 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. ) Tsujino , T. , Yoshida , K. , Nakayama , H. , Ito , H. , Shimosato , T. and Tahara , E.Alterations of oncogenes in metastatic tumours of human gastric carcinomas . Br. J. Cancer , 62 , 226 – 230 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. ) Tahara , E.Molecular mechanism of stomach carcinogenesis . J. Cancer Res. Clin. Oncol. , 119 , 265 – 272 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29. ) Dou , Q.‐P. , Levin , A. H. , Zhao , S. and Pardee , A. B.Cyclin E and cyclin A as candidates for the restriction point protein . Cancer Res. , 53 , 1493 – 1497 ( 1993. ). [PubMed] [Google Scholar]
  • 30. ) Japanese Research Society for Gastric Cancer . “ Japanese Classification of Gastric Carcinoma ,” First English edition ( 1995. ). Kanehara; , Tokyo . [Google Scholar]

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