Genetic determinants of p53-induced apoptosis and growth arrest

Kornelia Polyak, Todd Waldman, Tong Chuan He, Kenneth W Kinzler, Bert Vogelstein

Research output: Contribution to journalArticle

Abstract

Previous studies have suggested that expression of p53 in cancer cells can result in either growth arrest or apoptosis. Accordingly, expression of p53 in a series of colorectal cancer cell lines yielded growth arrest in some lines (A-lines) and apoptosis in others (D-lines). To investigate the basis of this difference, we evaluated the role of p21(WAF1/Cip1), a known mediator of p53-induced growth arrest. Inactivation of p21 by homologous recombination converted an A-line to a D-line, suggesting that p21 could protect cells from apoptosis. However, examination of p53-induced p21 expression in naturally occurring D-lines and A-lines demonstrated that the induction of p21 could not account for the differential response to p53. Moreover, when a D-line was fused to an A-line, the resulting hybrid cells underwent apoptosis in response to p53, indicating that the apoptosis pathway was dominant over the growth arrest pathway. Therefore, the apoptotic response to p53 in colorectal cancer cells is modulated by at least two factors: p21-mediated growth arrest that can protect cells from apoptosis in A-cells, and trans-acting factors in D-cells that can overcome this protection, resulting in cell death.

Original languageEnglish (US)
Pages (from-to)1945-1952
Number of pages8
JournalGenes & development
Volume10
Issue number15
StatePublished - 1996

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Apoptosis
Growth
Colorectal Neoplasms
Trans-Activators
Somatostatin-Secreting Cells
Hybrid Cells
Homologous Recombination
Cell Death
Cell Line
Neoplasms

Keywords

  • apoptosis
  • growth arrest
  • p21(WAF1/Cip1)
  • p53

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Genetic determinants of p53-induced apoptosis and growth arrest. / Polyak, Kornelia; Waldman, Todd; He, Tong Chuan; Kinzler, Kenneth W; Vogelstein, Bert.

In: Genes & development, Vol. 10, No. 15, 1996, p. 1945-1952.

Research output: Contribution to journalArticle

Polyak, Kornelia ; Waldman, Todd ; He, Tong Chuan ; Kinzler, Kenneth W ; Vogelstein, Bert. / Genetic determinants of p53-induced apoptosis and growth arrest. In: Genes & development. 1996 ; Vol. 10, No. 15. pp. 1945-1952.
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