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

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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

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Epithelial Cells
Apoptosis
Temperature
Cell Death
G1 Phase Cell Cycle Checkpoints
Serum
Alleles
Carcinoma
Kidney
Cell Line
Growth
Therapeutics

Keywords

  • Apoptosis
  • Epithelial cells
  • Myc
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Sakamuro, D., Eviner, V., Elliott, K. J., Showe, L., White, E., & Prendergast, G. C. (1995). c-Myc induces apoptosis in epithelial cells by both p53-dependent and p53-independent mechanisms. Oncogene, 11(11), 2410-2418.

c-Myc induces apoptosis in epithelial cells by both p53-dependent and p53-independent mechanisms. / Sakamuro, Daitoku; Eviner, Valerie; Elliott, Katherine J.; Showe, Louise; White, Eileen; Prendergast, George C.

In: Oncogene, Vol. 11, No. 11, 07.12.1995, p. 2410-2418.

Research output: Contribution to journalArticle

Sakamuro, D, Eviner, V, Elliott, KJ, Showe, L, White, E & Prendergast, GC 1995, 'c-Myc induces apoptosis in epithelial cells by both p53-dependent and p53-independent mechanisms', Oncogene, vol. 11, no. 11, pp. 2410-2418.
Sakamuro D, Eviner V, Elliott KJ, Showe L, White E, Prendergast GC. c-Myc induces apoptosis in epithelial cells by both p53-dependent and p53-independent mechanisms. Oncogene. 1995 Dec 7;11(11):2410-2418.
Sakamuro, Daitoku ; Eviner, Valerie ; Elliott, Katherine J. ; Showe, Louise ; White, Eileen ; Prendergast, George C. / c-Myc induces apoptosis in epithelial cells by both p53-dependent and p53-independent mechanisms. In: Oncogene. 1995 ; Vol. 11, No. 11. pp. 2410-2418.
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