This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Halvorsen, T. L.
Right arrow Articles by Levine, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Halvorsen, T. L.
Right arrow Articles by Levine, F.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 1999, p. 1864-1870, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Telomerase Activity Is Sufficient To Allow Transformed Cells To Escape from Crisis

Tanya L. Halvorsen, Gil Leibowitz, and Fred Levine*

Center for Molecular Genetics, University of California at San Diego, La Jolla, California 92093-0634

Received 20 July 1998/Returned for modification 28 August 1998/Accepted 23 November 1998

The introduction of simian virus 40 large T antigen (SVLT) into human primary cells enables them to proliferate beyond their normal replicative life span. In most cases, this temporary escape from senescence eventually ends in a second proliferative block known as "crisis," during which the cells cease growing or die. Rare immortalization events in which cells escape crisis are frequently correlated with the presence of telomerase activity. We tested the hypothesis that telomerase activation is the critical step in the immortalization process by studying the effects of telomerase activity in two mortal SVLT-Rasval12-transformed human pancreatic cell lines, TRM-6 and beta lox5. The telomerase catalytic subunit, hTRT, was introduced into late-passage cells via retroviral gene transfer. Telomerase activity was successfully induced in infected cells, as demonstrated by a telomerase repeat amplification protocol assay. In each of nine independent infections, telomerase-positive cells formed rapidly dividing cell lines while control cells entered crisis. Telomere lengths initially increased, but telomeres were then maintained at their new lengths for at least 20 population doublings. These results demonstrate that telomerase activity is sufficient to enable transformed cells to escape crisis and that telomere elongation in these cells occurs in a tightly regulated manner.

* Corresponding author. Mailing address: University of California, San Diego, Center for Molecular Genetics, Rm. 122, La Jolla, CA 92093-0634. Phone: (619) 534-5979. Fax: (619) 534-1422. E-mail: flevine{at}ucsd.edu.

Molecular and Cellular Biology, March 1999, p. 1864-1870, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Huang, X.-Q., Wang, J., Liu, J.-P., Feng, H., Liu, W.-B., Yan, Q., Liu, Y., Sun, S.-M., Deng, M., Gong, L., Liu, Y., Li, D. W.-C. (2005). hTERT Extends Proliferative Lifespan and Prevents Oxidative Stress-Induced Apoptosis in Human Lens Epithelial Cells. IOVS 46: 2503-2513 [Abstract] [Full Text]  
  • Wang, S., Zhu, J. (2004). The hTERT Gene Is Embedded in a Nuclease-resistant Chromatin Domain. J. Biol. Chem. 279: 55401-55410 [Abstract] [Full Text]  
  • Shahrabani-Gargir, L., Pandita, T. K., Werner, H. (2004). Ataxia-Telangiectasia Mutated Gene Controls Insulin-Like Growth Factor I Receptor Gene Expression in a Deoxyribonucleic Acid Damage Response Pathway via Mechanisms Involving Zinc-Finger Transcription Factors Sp1 and WT1. Endocrinology 145: 5679-5687 [Abstract] [Full Text]  
  • Taylor, L. M., James, A., Schuller, C. E., Brce, J., Lock, R. B., MacKenzie, K. L. (2004). 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. 279: 43634-43645 [Abstract] [Full Text]  
  • Ladetto, M., Compagno, M., Ricca, I., Pagano, M., Rocci, A., Astolfi, M., Drandi, D., di Celle, P. F., Dell'Aquila, M., Mantoan, B., Vallet, S., Pagliano, G., De Marco, F., Francese, R., Santo, L., Cuttica, A., Marinone, C., Boccadoro, M., Tarella, C. (2004). Telomere length correlates with histopathogenesis according to the germinal center in mature B-cell lymphoproliferative disorders. Blood 103: 4644-4649 [Abstract] [Full Text]  
  • Sipila, P., Shariatmadari, R., Huhtaniemi, I. T., Poutanen, M. (2004). Immortalization of Epididymal Epithelium in Transgenic Mice Expressing Simian Virus 40 T Antigen: Characterization of Cell Lines and Regulation of the Polyoma Enhancer Activator 3. Endocrinology 145: 437-446 [Abstract] [Full Text]  
  • Palanca-Wessels, M. C. A., Klingelhutz, A., Reid, B. J., Norwood, T. H., Opheim, K. E., Paulson, T. G., Feng, Z., Rabinovitch, P. S. (2003). Extended lifespan of Barrett's esophagus epithelium transduced with the human telomerase catalytic subunit: a useful in vitro model. Carcinogenesis 24: 1183-1190 [Abstract] [Full Text]  
  • Hahn, W. C. (2003). Role of Telomeres and Telomerase in the Pathogenesis of Human Cancer. JCO 21: 2034-2043 [Abstract] [Full Text]  
  • Hahn, W. C., Weinberg, R. A. (2002). Rules for Making Human Tumor Cells. NEJM 347: 1593-1603 [Full Text]  
  • Banik, S. S. R., Guo, C., Smith, A. C., Margolis, S. S., Richardson, D. A., Tirado, C. A., Counter, C. M. (2002). C-Terminal Regions of the Human Telomerase Catalytic Subunit Essential for In Vivo Enzyme Activity. Mol. Cell. Biol. 22: 6234-6246 [Abstract] [Full Text]  
  • Martin, J. A., Forest, E., Block, J. A., Klingelhutz, A. J., Whited, B., Gitelis, S., Wilkey, A., Buckwalter, J. A. (2002). Malignant Transformation in Human Chondrosarcoma Cells Supported by Telomerase Activation and Tumor Suppressor Inactivation. Cell Growth Differ. 13: 397-407 [Abstract] [Full Text]  
  • Demeterco, C., Itkin-Ansari, P., Tyrberg, B., Ford, L. P., Jarvis, R. A., Levine, F. (2002). c-Myc Controls Proliferation Versus Differentiation in Human Pancreatic Endocrine Cells. J. Clin. Endocrinol. Metab. 87: 3475-3485 [Abstract] [Full Text]  
  • Marcotte, R., Wang, E. (2002). Replicative Senescence Revisited. Journals of Gerontology Series A: Biological Sciences and Medical Sciences 57: B257-269 [Abstract] [Full Text]  
  • Hahn, W. C., Dessain, S. K., Brooks, M. W., King, J. E., Elenbaas, B., Sabatini, D. M., DeCaprio, J. A., Weinberg, R. A. (2002). Enumeration of the Simian Virus 40 Early Region Elements Necessary for Human Cell Transformation. Mol. Cell. Biol. 22: 2111-2123 [Abstract] [Full Text]  
  • Mergny, J.-L., Riou, J.-F., Mailliet, P., Teulade-Fichou, M.-P., Gilson, E. (2002). Natural and pharmacological regulation of telomerase. Nucleic Acids Res 30: 839-865 [Abstract] [Full Text]  
  • Darimont, C., Avanti, O., Tromvoukis, Y., Vautravers-Leone, P., Kurihara, N., Roodman, G. D., Colgin, L. M., Tullberg-Reinert, H., Pfeifer, A. M. A., Offord, E. A., Mace, K. (2002). SV40 T Antigen and Telomerase Are Required to Obtain Immortalized Human Adult Bone Cells without Loss of the Differentiated Phenotype. Cell Growth Differ. 13: 59-67 [Abstract] [Full Text]  
  • Goodwin, E. C., DiMaio, D. (2001). Induced Senescence in HeLa Cervical Carcinoma Cells Containing Elevated Telomerase Activity and Extended Telomeres. Cell Growth Differ. 12: 525-534 [Abstract] [Full Text]  
  • Alexander, K., Hinds, P. W. (2001). Requirement for p27KIP1 in Retinoblastoma Protein-Mediated Senescence. Mol. Cell. Biol. 21: 3616-3631 [Abstract] [Full Text]  
  • Shay, J. W., Zou, Y., Hiyama, E., Wright, W. E. (2001). Telomerase and cancer. Hum Mol Genet 10: 677-685 [Abstract] [Full Text]  
  • Dufayet de la Tour, D., Halvorsen, T., Demeterco, C., Tyrberg, B., Itkin-Ansari, P., Loy, M., Yoo, S.-J., Hao, E., Bossie, S., Levine, F. (2001). {beta}-Cell Differentiation from a Human Pancreatic Cell Line in Vitro and in Vivo. Mol. Endocrinol. 15: 476-483 [Abstract] [Full Text]  
  • Meyerson, M. (2000). Role of Telomerase in Normal and Cancer Cells. JCO 18: 2626-2634 [Abstract] [Full Text]  
  • Ouellette, M. M., Liao, M., Herbert, B.-S., Johnson, M., Holt, S. E., Liss, H. S., Shay, J. W., Wright, W. E. (2000). Subsenescent Telomere Lengths in Fibroblasts Immortalized by Limiting Amounts of Telomerase. J. Biol. Chem. 275: 10072-10076 [Abstract] [Full Text]  
  • Reddel, R. R. (2000). The role of senescence and immortalization in carcinogenesis. Carcinogenesis 21: 477-484 [Abstract] [Full Text]  
  • LIU, J.-P. (1999). Studies of the molecular mechanisms in the regulation of telomerase activity. FASEB J. 13: 2091-2104 [Abstract] [Full Text]  
  • Masutomi, K., Kaneko, S., Hayashi, N., Yamashita, T., Shirota, Y., Kobayashi, K., Murakami, S. (2000). Telomerase Activity Reconstituted in Vitro with Purified Human Telomerase Reverse Transcriptase and Human Telomerase RNA Component. J. Biol. Chem. 275: 22568-22573 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»