c-Myc induces apoptosis in epithelial cells by both p53-dependent and p53-independent mechanisms

Daitoku Sakamuro, Valerie Eviner, Katherine J. Elliott, Louise Showe, Eileen White, George C. Prendergast

Research output: Contribution to journalArticlepeer-review

154 Scopus citations

Abstract

We tested the hypothesis that wild-type p53 activity is required for c-Myc-dependent apoptosis in epithelial cells. Primary baby rat kidney epithelial cell lines were generated by immortalization through the concerted action of c-Myc and a temperature-sensitive (ts) dominant inhibitory mutant allele of p53 (BRK myc/p53ts cells). When shifted to the permissive temperature for wild-type p53 activity, the BRK myc/p53ts cells underwent growth arrest and apoptosis. However, apoptosis also could be induced by serum deprivation at the nonpermissive temperature, when p53 was in the mutant state. Bcl-2 suppressed both modes of cell death. Apoptosis induced by wild-type p53 but not by serum deprivation was accompanied by G1 cell cycle arrest and increased expression of the Bcl-2 antagonist Bax. We concluded that c-Myc could induce apoptosis in epithelial cells by at least two mechanisms that could be distinguished by their p53 requirement. Our results support the possibility that c-Myc-dependent cell death might be exploited for therapeutic ends during carcinoma development, without regard to p53 status of the target cell.

Original languageEnglish (US)
Pages (from-to)2410-2418
Number of pages9
JournalOncogene
Volume11
Issue number11
StatePublished - Dec 7 1995

Keywords

  • Apoptosis
  • Epithelial cells
  • Myc
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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