p53 codon 72 alleles influence the response to anticancer drugs in cells from aged people by regulating the cell cycle inhibitor p21WAF1

Stefano Salvioli, Massimiliano Bonafé, Cristiana Barbi, Gianluca Storci, Chiara Trapassi, Francesca Tocco, Silvia Gravina, Matteo Rossi, Luca Tiberi, Chiara Mondello, Daniela Monti, Claudio Franceschi

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43 Scopus citations

Abstract

A common polymorphism at codon 72 in p53 gene leads to an arginine to proline aminoacidic substitution which affects in an age-dependent manner the susceptibility of cells to undergo apoptosis after oxidative stress. Here we report that dermal fibroblasts from Proline allele carriers (Pro+) display a higher expression of p21 WAF1 gene, in both basal conditions and after treatment with doxorubicin or camptothecin. This phenomenon is accompanied by a lower susceptibility of Pro+ cells to undergo apoptosis, a lower capability to over cross G1-S transition and an increased propensity to express markers of cell senescence, with respect to fibroblasts from Arginine homozygotes (Pro-). All these phenomena are particularly evident in cells from centenarians. We conclude that the functional difference between the two p53 codon 72 alleles exerts a broad impact on the capability of cell from aged people to respond to stressors such as cytotoxic drugs.

Original languageEnglish (US)
Pages (from-to)1264-1271
Number of pages8
JournalCell Cycle
Volume4
Issue number9
DOIs
StatePublished - Sep 2005

Keywords

  • Apoptosis
  • Cell cycle
  • Cell senescence
  • p21WAF1
  • p53 codon 72 polymorphism

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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    Salvioli, S., Bonafé, M., Barbi, C., Storci, G., Trapassi, C., Tocco, F., Gravina, S., Rossi, M., Tiberi, L., Mondello, C., Monti, D., & Franceschi, C. (2005). p53 codon 72 alleles influence the response to anticancer drugs in cells from aged people by regulating the cell cycle inhibitor p21WAF1. Cell Cycle, 4(9), 1264-1271. https://doi.org/10.4161/cc.4.9.1978