Abrogation of oncogene-associated apoptosis allows transformation of p53-deficient cells - PubMed (original) (raw)

Abrogation of oncogene-associated apoptosis allows transformation of p53-deficient cells

S W Lowe et al. Proc Natl Acad Sci U S A. 1994.

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.

PubMed Disclaimer

References

    1. Nature. 1980 Apr 10;284(5756):555-6 - PubMed
    1. Cell. 1993 Sep 24;74(6):957-67 - PubMed
    1. Nature. 1984 Dec 13-19;312(5995):651-4 - PubMed
    1. Mol Cell Biol. 1984 Dec;4(12):2929-31 - PubMed
    1. Anticancer Res. 1985 Jan-Feb;5(1):131-6 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources