Induced p53 expression in lung cancer cell line promotes cell senescence and differentially modifies the cytotoxicity of anti-cancer drugs

Yingcai Wang, Giovanni Blandino, Moshe Oren, David Givol

Research output: Contribution to journalArticle

Abstract

The p53-null human lung cancer cell line H1299 was used in order to generate clones with ecdysone-inducible p53 as well as ecdysone-inducible p21(waf1). Induced expression of p53 resulted in irreversible cell growth arrest with characteristics of replicative senescence, suggesting that p53 can prevent immortalization by activating a senescence program. The effect of induced p53 and p21(waf1) expression on the cytotoxic action of the anti-cancer drugs etoposide and cisplatin was also analysed. Whereas p21(waf1) overexpression conferred increased resistance to killing by either drug, p53 overexpression enhanced the cytotoxic effect of cisplatin but protected against etoposide cytotoxicity. These results imply that the impact of p53 on susceptibility to chemotherapy may depend greatly on the particular drug and type of DNA damage. Moreover, these data demonstrate the importance of using isogenic cell lines to address this issue.

Original languageEnglish
Pages (from-to)1923-1930
Number of pages8
JournalOncogene
Volume17
Issue number15
Publication statusPublished - Oct 15 1998

Keywords

  • Anti-cancer drugs
  • Inducible p53
  • p21(waf1)
  • Senescence

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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