HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 9, 7692-7698, February 28, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/9/7692    most recent M212944200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gorbunova, V. Articles by Pereira-Smith, O. M. Search for Related Content PubMed PubMed Citation Articles by Gorbunova, V. Articles by Pereira-Smith, O. M. Social Bookmarking                      What's this?

Evidence That High Telomerase Activity May Induce a Senescent-like Growth Arrest in Human Fibroblasts^*

Vera Gorbunova, Andrei Seluanov, and Olivia M. Pereira-Smith^§

From the Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030

Expression of the catalytic subunit of human telomerase (hTERT), in normal human fibroblasts allows them to escape replicative senescence. However, we have observed that populations of hTERT-immortalized human fibroblasts contain 3-20% cells with a senescent morphology. To determine what causes the appearance of these senescent-like cells, we used flow cytometry to select them from the population and analyzed them for various senescence markers, telomere length, and telomerase activity. This subpopulation of cells had elevated levels of p21 and hypophosphorylated Rb, but telomere length was similar to that of the immortal cells in the culture that was sorted. Surprisingly, telomerase activity in the senescent-like cells was significantly elevated compared with immortal cells from the same population, suggesting that high telomerase activity may induce the senescent phenotype. Furthermore, transfection of normal fibroblasts with a hTERT-expressing plasmid that confers high telomerase activity led to the induction of p21, a higher percentage of SA--galactosidase-positive cells, and a greater number of cells entering growth arrest compared with controls. These results suggest that excessive telomerase activity may act as a hyperproliferative signal in cells and induce a senescent phenotype in a manner similar to that seen following overexpression of oncogenic Ras, Raf, and E2F1. Thus, there must be a critical threshold of telomerase activity that permits cell proliferation.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				O. Menzel, M. Migliaccio, D. R. Goldstein, S. Dahoun, M. Delorenzi, and N. Rufer Mechanisms Regulating the Proliferative Potential of Human CD8+ T Lymphocytes Overexpressing Telomerase J. Immunol., September 15, 2006; 177(6): 3657 - 3668. [Abstract] [Full Text] [PDF]

				J. H. Santos, J. N. Meyer, and B. Van Houten Mitochondrial localization of telomerase as a determinant for hydrogen peroxide-induced mitochondrial DNA damage and apoptosis Hum. Mol. Genet., June 1, 2006; 15(11): 1757 - 1768. [Abstract] [Full Text] [PDF]

				N. F. Lue, D. Bosoy, T. J. Moriarty, C. Autexier, B. Altman, and S. Leng Telomerase can act as a template- and RNA-independent terminal transferase PNAS, July 12, 2005; 102(28): 9778 - 9783. [Abstract] [Full Text] [PDF]

				M. Ferenac, D. Polancec, M. Huzak, O. M. Pereira-Smith, and I. Rubelj Early-Senescing Human Skin Fibroblasts Do Not Demonstrate Accelerated Telomere Shortening J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2005; 60(7): 820 - 829. [Abstract] [Full Text] [PDF]

				L. M. Taylor, A. James, C. E. Schuller, J. Brce, R. B. Lock, and K. L. MacKenzie Inactivation of p16INK4a, with Retention of pRB and p53/p21cip1 Function, in Human MRC5 Fibroblasts That Overcome a Telomere-independent Crisis during Immortalization J. Biol. Chem., October 15, 2004; 279(42): 43634 - 43645. [Abstract] [Full Text] [PDF]

				C. Martin-Ruiz, G. Saretzki, J. Petrie, J. Ladhoff, J. Jeyapalan, W. Wei, J. Sedivy, and T. von Zglinicki Stochastic Variation in Telomere Shortening Rate Causes Heterogeneity of Human Fibroblast Replicative Life Span J. Biol. Chem., April 23, 2004; 279(17): 17826 - 17833. [Abstract] [Full Text] [PDF]