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

Lowe SW, Jacks T, Housman DE, Ruley HE
Proc Natl Acad Sci U S A. 1994 91 (6): 2026-30

PMID: 8134344 · PMCID: PMC43302 · DOI:10.1073/pnas.91.6.2026

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.

MeSH Terms (12)

Adenovirus E1A Proteins Animals Apoptosis Cell Division Cell Line Cell Transformation, Neoplastic Fibroblasts Male Mice Mice, Nude Oncogenes Tumor Suppressor Protein p53

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