Disparate effects of telomere attrition on gene expression during replicative senescence of human mammary epithelial cells cultured under different conditions

Hong Zhang, Brittney Shea Herbert, Kuang Hung Pan, Jerry W. Shay, Stanley N. Cohen

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Telomere shortening in populations of human mammary epithelial cells (HMECs) that survive early replicative arrest (MO) by the inactivation of p16INK4A during cell culture on plastic dishes leads to a state of permanent replicative arrest termed senescence. While culture of HMECs on feeder layers abrogates M0 and p16INK4A inactivation, progressive telomere attrition in these cells also eventually results in permanent replicative arrest. Expression of telomerase prevents both senescence on plastic (S-P) and senescence on feeder layers (S-FL) in HMECs, as it does also in cultured primary human fibroblasts. We report here that the gene expression profiles of senescence in HMECs of the same lineage maintained under different culture conditions showed surprisingly little commonality. Moreover, neither of these senescence-associated profiles in HMECs resembles the profile for senescence in human fibroblasts. These results indicate that senescence-associated alterations in gene expression resulting from telomere attrition are affected by culture conditions as well as by cell origins, and argue that replicative senescence at the molecular level is a diverse rather than unique cellular process.

Original languageEnglish (US)
Pages (from-to)6193-6198
Number of pages6
JournalOncogene
Volume23
Issue number37
DOIs
StatePublished - Aug 19 2004

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Keywords

  • Culture conditions
  • Mammary epithelial cells
  • Microarray
  • Replicative senescence
  • Telomere shortening

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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