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

Abstract

Telomere shortening in populations of human mammary epithelial cells (HMECs) that survive early replicative arrest (M0) 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.

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Acknowledgements

We thank Y Teng and R Lin for excellent technical assistance. This work was supported by Postdoctoral Fellowship 5FB-0067 from the California Breast Cancer Research Program to HZ, Postdoctoral Fellowship DAMD17-00-1-0438 from the Department of Defense Breast Cancer Research Program to BH and by grants from National Foundation for Cancer Research and The Ellison Foundation for Biomedical Research to SNC, and by AG07992 and CA70907 to JWS.

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Correspondence to Stanley N Cohen.

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Zhang, H., Herbert, BS., Pan, KH. et al. Disparate effects of telomere attrition on gene expression during replicative senescence of human mammary epithelial cells cultured under different conditions. Oncogene 23, 6193–6198 (2004). https://doi.org/10.1038/sj.onc.1207834

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