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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1997 Jan;88(1):49–55. doi: 10.1111/j.1349-7006.1997.tb00301.x

Expression of Fas Antigen and Its Mediation of Apoptosis in Human Gastric Cancer Cell Lines

Hisae Hayashi 1,, Shigeru Tatebe 1, Mitsuhiko Osaki 1, Akira Goto 1, Yoshimasa Suzuki 2, Hisao Ito 1
PMCID: PMC5921244  PMID: 9045896

Abstract

Fas, a member of the tumor necrosis factor receptor/nerve growth factor receptor family, induces apoptosis by crosslinking with Fas ligand or anti‐Fas antibody in a variety of cultured cells. We examined the expression of Fas antigen and its mediation of apoptosis in six human gastric carcinoma cell lines. Flow cytometric analysis and western blotting revealed relatively high expression of Fas antigen in MKN‐74 (wild‐type p53 gene) and MKN‐45 (wild‐type), followed by MKN‐1 (mutated), MKN‐7 (mutated) and KATO‐III (deleted). MKN‐28 (mutated) showed minimal expression of the antigen. The expression was apparently enhanced by interferon‐γ, except for MKN‐1 and MKN‐28. Anti‐Fas antibody (100 ng/ml) induced nuclear fragmentation characteristic of apoptosis. Apoptosis occurred in a delayed fashion and the apoptotic index at 72 h was approximately 60% in MKN‐74, 35% in MKN‐45, and 20% in MKN‐1 and KATO‐III. A DNA ladder was noted in MKN‐74 at 72 h. Expression levels of P53 and P21Wafl did not change for up to 48 h in MKN‐74. The biological effects did not correlate with endogenous Bcl‐2 expression. These results indicated that a) Fas antigen is variably expressed in human cultured gastric carcinoma cells, b) the protein transduces an apoptotic signal which leads to delayed cell death, and c) susceptibility to the antibody correlates well with the expression level of Fas antigen.

Keywords: Apoptosis, Fas, Human gastric cancer cell line

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REFERENCES

  • 1. ) Kerr , J. F. R. , Wyllie , A. H. and Currie , A. A.Apoptosis: a basic biological phenomenon with wide‐ranging implications in tissue kinetics . Br. J. Cancer , 26 , 239 – 257 ( 1972. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. ) Kerr , J. F. R. , Winterford , C. M. and Harmon , B. V.Apoptosis. Its significance in cancer and cancer therapy . Cancer , 73 , 2013 – 2026 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Majno , G. and Joris , I.Apoptosis, oncosis, and necrosis. An overview of cell death . Am.J.Pathol , 146 , 3 – 15 ( 1995. ). [PMC free article] [PubMed] [Google Scholar]
  • 4. ) Wyllie , A. H. , Morris , R. G. , Smith , A. L. and Dunlop , D.Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macro‐molecular synthesis . J. Pathol. , 142 , 67 – 77 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Steller , H.Mechanisms and genes of cellular suicide . Science , 267 , 1445 – 1449 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Shimamura , A. and Fisher , D. E.p53 in life and death . Clin. Cancer Res. , 2 , 435 – 440 ( 1996. ). [PubMed] [Google Scholar]
  • 7. ) Bargou , R. C. , Daniel , P. T. , Mapara , M. Y. , Bommert , K. , Wagener , C. , Kallinich , B. , Royer , H. D. and Dörken , B.Expression of the bcl‐2 gene family in normal and malignant breast tissue: low bax‐α expression in tumor cells correlates with resistance towards apoptosis . Int. J. Cancer , 60 , 854 – 859 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Nagata , S. and Golstein , P.The Fas death factor . Science , 267 , 1449 – 1456 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Yonehara , S. , Ishii , A , and Yonehara , M.A cell‐killing monoclonal antibody (anti‐Fas) to a cell surface antigen co‐downregulated with the receptor of tumor necrosis factor . J. Exp. Med. , 169 , 1747 – 1756 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. ) Watanabe‐Fukunaga , R. , Brannan , C. I. , Itoh , N. , Yonehara , S. , Copeland , N. G. , Jenkins , N. A. and Nagata , S.The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen . J. Immunol , 148 , 1274 – 1279 ( 1992. ). [PubMed] [Google Scholar]
  • 11. ) Itoh , N. , Yonehara , S. , Ishii , A. , Yonehara , M. , Mizushima , S‐I. , Sameshima , M. , Hase , A. , Seto , Y. and Nagata , S.The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis . Cell 66 , 233 – 243 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Trauth , B. C. , Klas , C. , Peters , A. M. J. , Matzku , S. , Möller , P. , Falk , W. , Debatin , K.‐M. and Krammer , P. H.Monoclonal antibody‐mediated tumor regression by induction of apoptosis . Science , 245 , 301 – 305 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Owen‐Schaub , L. B. , Yonehara , S. , Crump , IIIW. L. and Grimm , E. A.DNA fragmentation and cell death is selectively triggered in activated human lymphocytes by Fas antigen engagement . Cell. Immunol , 140 , 197 – 205 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Miyawaki , T. , Uehara , T. , Nibu , R. , Tsuji , T. , Yachie , A. , Yonehara , S. and Taniguchi , N.Differential expression of apoptosis‐related Fas antigen on lymphocyte subpopulations in human peripheral blood . J. Immunol. , 149 , 3753 – 3758 ( 1992. ). [PubMed] [Google Scholar]
  • 15. ) Itoh , N. , Tsujimoto , Y. and Nagata , S.Effect of bcl‐2 on Fas antigen‐mediated cell death . J. Immunol. , 151 , 621 – 627 ( 1993. ). [PubMed] [Google Scholar]
  • 16. ) Lacronique , V. , Mignon , A. , Fabre , M. , Viollet , B. , Rouquet , N. , Molina , T. , Porteu , A. , Henrion , A. , Bouscary , D. , Varlet , P. , Joulin , V. and Kahn , A.Bcl‐2 protects from lethal hepatic apoptosis induced by an anti‐Fas antibody in mice . Nat Med. , 2 , 80 – 86 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Owen‐Schaub , L. B. , Radinsky , R. , Kruzel , E. , Berry , K. and Yonehara , S.Anti‐Fas on nonhematopoietic tumors: levels of Fas/APO‐1 and bcl‐2 are not predictive of biological responsiveness . Cancer Res. , 54 , 1580 – 1586 ( 1994. ). [PubMed] [Google Scholar]
  • 18. ) Mattar , R. , Yokozaki , H. , Yasui , W. , Ito , H. and Tahara , E.P53 gene mutation in gastric cancer cell lines . Oncology (Life Sci. Adv.) , 11 , 127 – 132 ( 1992. ). [Google Scholar]
  • 19. ) Westendorf , J. J. , Lammert , J. M. and Jelinek , D. F.Expression and function of Fas (APO‐1/CD95) in patient myeloma cells and myeloma cell lines . Blood , 85 , 3566 – 3576 ( 1995. ). [PubMed] [Google Scholar]
  • 20. ) Tamura , T. , Aoyama , N. , Saya , H. , Haga , H. , Futami , S. , Miyamoto , M. , Koh , T. , Ariyasu , T. , Tachi , M. , Kasuga , M. and Takahashi , R.Induction of Fas‐mediated apoptosisinp53‐transfectedhumancoloncarcinoma cells . Oncogene , 11 , 1939 – 1946 ( 1995. ). [PubMed] [Google Scholar]
  • 21. ) Haapajarvi , T. , Kivinen , L. , Pitkanen , K. and Laiho , M.Cell cycle dependent effects of U.V.‐radiation on p53 expression and retinoblastoma protein phosphorylation . Oncogene , 11 , 151 – 159 ( 1995. ). [PubMed] [Google Scholar]
  • 22. ) Rosselli , F. , Ridet , A. , Soussi , T. , Duchaud , E. , Alapetite , C. and Moustacchi , E.p53‐dependent pathway of radio‐induced apoptosis is altered in Fanconi anemia . Oncogene , 10 , 9 – 17 ( 1995. ). [PubMed] [Google Scholar]
  • 23. ) Ni , R. , Tomita , Y. , Matuda , K. , Ichihara , A. , Ishimura , K. , Ogasawara , J. and Nagata , S.Fas‐mediated apoptosis in primary cultured mouse hepatocytes . Exp. Cell Res. , 215 , 332 – 337 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 24. ) Enari , M. , Hug , H. and Nagata , S.Involvement of an ICE‐Iike protease in Fas‐mediated apoptosis . Nature , 375 , 78 – 81 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Los , M. , Van‐de‐Craen , M. , Penning , L. C. , Schenk , H. , Westendorp , M. , Baeuerle , P. A. , Dröge , W. , Krammer , P. H. , Fiers , W. and Schulze‐Osthoff , K.Requirement of an ICE/CED‐3 protease for Fas/APO‐1‐mediated apoptosis . Nature , 375 , 81 – 83 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Jaattela , M. , Benedict , M. , Tewari , M. , Shayman , J. A. and Dixit , V. M.Bcl‐X and Bcl‐2 inhibit TNF and Fas‐induced apoptosis and activation of phospholipase A2 inbreastcarcinomacells . Oncogene , 10 , 2297 – 2305 ( 1995. ). [PubMed] [Google Scholar]
  • 27. ) Mapara , M.Y. , Bargou , R. , Zugck , C. , Döhner , H. , Ustaoglu , F. , Jonker , R. R. , Krammer , P. H. and Dörken , B.Apo‐1 mediated apoptosis or proliferation in human chronic B lymphocytic leukemia: correlation with bcl‐2 Oncogeneexpression . Eur. J. Immunol , 23 , 702 – 708 ( 1993. ). [DOI] [PubMed] [Google Scholar]

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