Abrogation of Oncogene-associated Apoptosis Allows Transformation of P53-deficient Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1994 Mar 15

PMID 8134344

Citations 89

Authors

S W Lowe

T Jacks

D E Housman

H E Ruley

Affiliations

Soon will be listed here.

Abstract

p53-deficient mouse embryonic fibroblasts were used to establish a direct mechanism of tumor suppression by p53 involving the destruction of oncogene-expressing cells by apoptosis. The absence of p53 enhanced cell growth, appeared sufficient for immortalization, and allowed a single oncogene [adenovirus early region 1A (E1A)] to transform cells to a tumorigenic state. p53 suppressed transformation of E1A-expressing cells by apoptosis. Apoptosis was associated with p53 stabilization and was triggered by environmental signals that normally suppress cell growth. Absence of even a single p53 allele significantly enhanced cell growth and survival. Although abrogation of apoptosis allowed transformation by E1A alone, escape from apoptosis susceptibility was not a prerequisite for tumor growth. Consequently, p53 mutation could enhance the survival of malignant cells expressing oncogenes activated early in tumor progression.

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