Induction of Fas-mediated apoptosis in p53-transfected human colon carcinoma cells

T. Tamura, N. Aoyama, H. Saya, H. Haga, S. Futami, M. Miyamoto, T. Koh, T. Ariyasu, M. Tachi, M. Kasuga, R. Takahashi

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Abstract

To investigate the biological function of p53 in colon carcinoma cells, a wild-type p53 expression plasmid under the control of the human cytomegalovirus promoter was stably transfected into the human colon adenocarcinoma cell line WiDr, which carries a mutation of the p53 gene at codon 273. Exogenous wild-type p53 transcripts were detected at various expression levels in 8 of 117 G418-resistant clones. The growth rates of the wild-type p53+ clones in culture did not change significantly. The efficiency of colony formation in soft agar, however, was completely suppressed in two wild-type p53+ clones. This is the first to demonstrate the feasibility of stable transfection of the wild-type p53 gene under the control of non-inducible promoter in human colon cancer cells. The major alteration found was that wild-type p53+ cells which were incubated with anti-Fas IgM showed marked cytolysis with preferential overexpression of wild-type p53 accompanied by overexpression of a cyclin-dependent kinase inhibitor, WAF1, whereas the endogenous mutant p53 retained its expression level. The findings suggest that a Fas-initiated pathway is incidentally linked to a p53-dependent apoptotic pathway through the reconstituted wild-type p53 gene in WiDr cells. This model should help elucidating the additional role of the p53 tumor suppressor gene and the mechanism of apoptosis in colon carcinoma cells.

Original languageEnglish
Pages (from-to)1939-1946
Number of pages8
JournalOncogene
Volume11
Issue number10
Publication statusPublished - 1995 Jan 1

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Keywords

  • Apoptosis
  • Colon cancer
  • Fas
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Tamura, T., Aoyama, N., Saya, H., Haga, H., Futami, S., Miyamoto, M., Koh, T., Ariyasu, T., Tachi, M., Kasuga, M., & Takahashi, R. (1995). Induction of Fas-mediated apoptosis in p53-transfected human colon carcinoma cells. Oncogene, 11(10), 1939-1946.