Activation of p53/p21(waf1) pathway is associated with senescence during v-Ha-ras transformation of immortal C2C12 myoblasts

G. D'Orazi, S. Soddu, A. Sacchi

Research output: Contribution to journalArticle

Abstract

It has recently been shown that tumor cells can retain the ability to undergo senescence, while the capacity of by-passing senescence has been associated with tumor progression. In this report, we showed that v-Ha-ras-mediated transformation of already immortal C2C12 myoblasts can be associated with senescence, in a low amount during in vitro passages and, to a higher extent, affer cellular stress (cell culture alkalinkation), or DNA damage (doxorubicin treatment). The capacity to undergo replicative senescence is associated with a strong increase of wtp53 transcriptional activity and p21(WAF1) up-regulation. These biochemical activities are down-modulated in the cells that evade the massive replicative senescence after stressing stimuli. Altogether, these findings show that active ras can cause senescence during the transformation of already immortal cells in association with p53/p21(WAF1) pathway activation and support the hypothesis that p53/p21(WAF1) functional activity is important in maintaining the integrity of the senescence pathway during cellular transformation.

Original languageEnglish
Pages (from-to)3497-3502
Number of pages6
JournalAnticancer Research
Volume20
Issue number5 B
Publication statusPublished - 2000

Keywords

  • p21(waf1)
  • p53
  • Replicative senescence
  • SA-beta-galactosidase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Activation of p53/p21(waf1) pathway is associated with senescence during v-Ha-ras transformation of immortal C2C12 myoblasts'. Together they form a unique fingerprint.

  • Cite this