Cancer Letters
Volume 194, Issue 2 , Pages 199-208, 15 May 2003

Human epithelial cell immortalization as a step in carcinogenesis

Lawrence Berkeley National Laboratory, Life Sciences Division, University of California, 1 Cyclotron Road, 70A1118, Berkeley, CA 94720-8174, USA

Received 10 September 2002; received in revised form 29 October 2002; accepted 29 October 2002.

Abstract 

Human epithelial cells encounter two senescence barriers that enforce a limited proliferative potential. A first barrier is mediated by the retinoblastoma protein, and can be overcome by multiple types of errors, many of which are observed in human cancers. A second, extremely stringent telomere-dependent barrier, is a consequence of repression of telomerase activity. Although relieved by ectopic hTERT expression, the nature of the errors required to overcome this latter barrier during in vivo carcinogenesis have not yet been defined. Attainment of immortality and telomerase reactivation are crucial to human carcinoma development; the derangements responsible for attainment of immortality may be rate-limiting and permissive for further progression to malignancy.

Telomerase, Telomere, p53, Epithelial cell, Immortalization, Senescence, Agonescence, Conversion, Tumor, Cancer, Oncogenesis, Tumorigenesis, Tumor suppressor

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PII: S0304-3835(02)00707-3

doi:10.1016/S0304-3835(02)00707-3

Cancer Letters
Volume 194, Issue 2 , Pages 199-208, 15 May 2003