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

par Salvioli, Stefano;Bonafé, Massimiliano;Barbi, Cristiana;Storci, Gianluca;Trapassi, Chiara;Tocco, Francesca;Gravina, Silvia;Rossi, Matteo;Tiberi, Luca ;Mondello, Chiara;Monti, Daniela;Franceschi, Claudio
Référence Cell Cycle, 4, 9, page (1264-1271)
Publication Publié, 2005-09

Article révisé par les pairs

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Résumé :

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. ©2005 Landes Bioscience.