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 Vaziri, H.
Right arrow Articles by Benchimol, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vaziri, H.
Right arrow Articles by Benchimol, S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 1999, p. 2373-2379, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Analysis of Genomic Integrity and p53-Dependent G1 Checkpoint in Telomerase-Induced Extended-Life-Span Human Fibroblasts

Homayoun Vaziri,1,* Jeremy A. Squire,2 Tej K. Pandita,3 Grace Bradley,2 Robert M. Kuba,2 Haihua Zhang,2 Sandor Gulyas,2 Richard P. Hill,2 Garry P. Nolan,1 and Samuel Benchimol2

Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305-53321; Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G-2M9, Canada2; and Center for Radiological Research, Columbia University, New York, New York 100323

Received 2 November 1998/Accepted 9 December 1998

Life span determination in normal human cells may be regulated by nucleoprotein structures called telomeres, the physical ends of eukaryotic chromosomes. Telomeres have been shown to be essential for chromosome stability and function and to shorten with each cell division in normal human cells in culture and with age in vivo. Reversal of telomere shortening by the forced expression of telomerase in normal cells has been shown to elongate telomeres and extend the replicative life span (H. Vaziri and S. Benchimol, Curr. Biol. 8:279-282, 1998; A. G. Bodnar et al., Science 279:349-352, 1998). Extension of the life span as a consequence of the functional inactivation of p53 is frequently associated with loss of genomic stability. Analysis of telomerase-induced extended-life-span fibroblast (TIELF) cells by G banding and spectral karyotyping indicated that forced extension of the life span by telomerase led to the transient formation of aberrant structures, which were subsequently resolved in higher passages. However, the p53-dependent G1 checkpoint was intact as assessed by functional activation of p53 protein in response to ionizing radiation and subsequent p53-mediated induction of p21Waf1/Cip1/Sdi1. TIELF cells were not tumorigenic and had a normal DNA strand break rejoining activity and normal radiosensitivity in response to ionizing radiation.

* Corresponding author. Mailing address: Stanford University School of Medicine, Department of Molecular Pharmacology, Edward's Building, 300 Pasteur Dr., Stanford, CA 94305-5332. Phone: (650) 498-4398. Fax: (650) 725-2952. E-mail: vaziri{at}cmgm.stanford.edu.

Molecular and Cellular Biology, March 1999, p. 2373-2379, 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:

  • Gillies, R. J., Robey, I., Gatenby, R. A. (2008). Causes and Consequences of Increased Glucose Metabolism of Cancers. JNM 49: 24S-42S [Abstract] [Full Text]  
  • Mahale, A. M., Khan, Z. A.T., Igarashi, M., Nanjangud, G. J., Qiao, R. F., Yao, S., Lee, S. W., Aaronson, S. A. (2008). Clonal Selection in Malignant Transformation of Human Fibroblasts Transduced with Defined Cellular Oncogenes. Cancer Res. 68: 1417-1426 [Abstract] [Full Text]  
  • Schreurs, M. W. J., Hermsen, M. A. J. A., Geltink, R. I. K., Scholten, K. B. J., Brink, A. A. T. P., Kueter, E. W. M., Tijssen, M., Meijer, C. J. L. M., Ylstra, B., Meijer, G. A., Hooijberg, E. (2005). Genomic stability and functional activity may be lost in telomerase-transduced human CD8+ T lymphocytes. Blood 106: 2663-2670 [Abstract] [Full Text]  
  • Krikun, G., Mor, G., Alvero, A., Guller, S., Schatz, F., Sapi, E., Rahman, M., Caze, R., Qumsiyeh, M., Lockwood, C. J. (2004). A Novel Immortalized Human Endometrial Stromal Cell Line with Normal Progestational Response. Endocrinology 145: 2291-2296 [Abstract] [Full Text]  
  • Scott, L. A., Vass, J. K., Parkinson, E. K., Gillespie, D. A. F., Winnie, J. N., Ozanne, B. W. (2004). Invasion of Normal Human Fibroblasts Induced by v-Fos Is Independent of Proliferation, Immortalization, and the Tumor Suppressors p16INK4a and p53. Mol. Cell. Biol. 24: 1540-1559 [Abstract] [Full Text]  
  • Sharma, G. G., Hwang, K.-k., Pandita, R. K., Gupta, A., Dhar, S., Parenteau, J., Agarwal, M., Worman, H. J., Wellinger, R. J., Pandita, T. K. (2003). Human Heterochromatin Protein 1 Isoforms HP1Hs{alpha} and HP1Hs{beta} Interfere with hTERT-Telomere Interactions and Correlate with Changes in Cell Growth and Response to Ionizing Radiation. Mol. Cell. Biol. 23: 8363-8376 [Abstract] [Full Text]  
  • Patry, C., Bouchard, L., Labrecque, P., Gendron, D., Lemieux, B., Toutant, J., Lapointe, E., Wellinger, R., Chabot, B. (2003). Small Interfering RNA-Mediated Reduction in Heterogeneous Nuclear Ribonucleoparticule A1/A2 Proteins Induces Apoptosis in Human Cancer Cells but not in Normal Mortal Cell Lines. Cancer Res. 63: 7679-7688 [Abstract] [Full Text]  
  • Milyavsky, M., Shats, I., Erez, N., Tang, X., Senderovich, S., Meerson, A., Tabach, Y., Goldfinger, N., Ginsberg, D., Harris, C. C., Rotter, V. (2003). Prolonged Culture of Telomerase-Immortalized Human Fibroblasts Leads to a Premalignant Phenotype. Cancer Res. 63: 7147-7157 [Abstract] [Full Text]  
  • Chigira, S., Sugita, K., Kita, K., Sugaya, S., Arase, Y., Ichinose, M., Shirasawa, H., Suzuki, N. (2003). Increased Expression of the Huntingtin Interacting Protein-1 Gene in Cells From Hutchinson Gilford Syndrome (Progeria) Patients and Aged Donors. Journals of Gerontology Series A: Biological Sciences and Medical Sciences 58: B873-878 [Abstract] [Full Text]  
  • Davalos, A. R., Campisi, J. (2003). Bloom syndrome cells undergo p53-dependent apoptosis and delayed assembly of BRCA1 and NBS1 repair complexes at stalled replication forks. JCB 162: 1197-1209 [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]  
  • Wieler, S., Gagne, J.-P., Vaziri, H., Poirier, G. G., Benchimol, S. (2003). Poly(ADP-ribose) Polymerase-1 Is a Positive Regulator of the p53-mediated G1 Arrest Response following Ionizing Radiation. J. Biol. Chem. 278: 18914-18921 [Abstract] [Full Text]  
  • Gorbunova, V., Seluanov, A., Pereira-Smith, O. M. (2003). Evidence That High Telomerase Activity May Induce a Senescent-like Growth Arrest in Human Fibroblasts. J. Biol. Chem. 278: 7692-7698 [Abstract] [Full Text]  
  • Itahana, K., Zou, Y., Itahana, Y., Martinez, J.-L., Beausejour, C., Jacobs, J. J. L., van Lohuizen, M., Band, V., Campisi, J., Dimri, G. P. (2003). Control of the Replicative Life Span of Human Fibroblasts by p16 and the Polycomb Protein Bmi-1. Mol. Cell. Biol. 23: 389-401 [Abstract] [Full Text]  
  • Huot, T. J., Rowe, J., Harland, M., Drayton, S., Brookes, S., Gooptu, C., Purkis, P., Fried, M., Bataille, V., Hara, E., Newton-Bishop, J., Peters, G. (2002). Biallelic Mutations in p16INK4a Confer Resistance to Ras- and Ets-Induced Senescence in Human Diploid Fibroblasts. Mol. Cell. Biol. 22: 8135-8143 [Abstract] [Full Text]  
  • Condon, J., Yin, S., Mayhew, B., Word, R. A., Wright, W.E., Shay, J.W., Rainey, W. E. (2002). Telomerase Immortalization of Human Myometrial Cells. Biol. Reprod. 67: 506-514 [Abstract] [Full Text]  
  • Maser, R. S., DePinho, R. A. (2002). Connecting Chromosomes, Crisis, and Cancer. Science 297: 565-569 [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]  
  • Roques, C. N., Boyer, J. C., Farber, R. A. (2001). Microsatellite Mutation Rates Are Equivalent in Normal and Telomerase-immortalized Human Fibroblasts. Cancer Res. 61: 8405-8407 [Abstract] [Full Text]  
  • Pritchard, D. E., Ceryak, S., Ha, L., Fornsaglio, J. L., Hartman, S. K., O'Brien, T. J., Patierno, S. R. (2001). Mechanism of Apoptosis and Determination of Cellular Fate in Chromium(VI)-exposed Populations of Telomerase-immortalized Human Fibroblasts. Cell Growth Differ. 12: 487-496 [Abstract] [Full Text]  
  • Ford, L. P., Suh, J. M., Wright, W. E., Shay, J. W. (2000). Heterogeneous Nuclear Ribonucleoproteins C1 and C2 Associate with the RNA Component of Human Telomerase. Mol. Cell. Biol. 20: 9084-9091 [Abstract] [Full Text]  
  • Meyerson, M. (2000). Role of Telomerase in Normal and Cancer Cells. JCO 18: 2626-2634 [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]  


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