Document Detail


Termination of lifespan of SV40-transformed human fibroblasts in crisis is due to apoptosis.
MedLine Citation:
PMID:  11857449     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Normal human fibroblasts in culture have a limited lifespan, ending in replicative senescence. Introduction of SV40 sequences encoding large T antigen and small t antigen into pre-senescent cells results in an extension of lifespan for an additional 20-30 population doublings. Rare clones of SV40-transformed cells are capable of indefinite growth and are described as immortal; however, the great majority of SV40-transformed cells terminate this extended lifespan in cell death, termed "crisis." We have examined the properties of cells in crisis to obtain further insights into mechanism of cell death and immortalization. Populations at the terminal cell passage show a balance between cell replication and cell death over a period of several weeks, with a progressive increase in cells undergoing cell death. During this period, there is less than a 3-fold increase in attached cell number, with two stages being identifiable on the basis of the focal pattern of cell survival. We also demonstrate that cells in crisis are undergoing apoptosis based on TUNEL assay, subG1 DNA content, annexin V reactivity, and activation of caspases 3 and 8. We suggest a model whereby SV40-transformed cells acquire increased sensitivity to apoptosis based on changes in properties which activate caspase 8 in addition to changes previously described involving shortening of telomeric sequences. While only telomere stabilization could be clearly shown to be essential for survival of cells through crisis, the extended period of cell replication and altered gene expression observed in SV40-transformed cells during crisis are compatible with other genetic alterations in immortal cells.
Authors:
Lisa Macera-Bloch; JeanMarie Houghton; Melanie Lenahan; Krishna K Jha; Harvey L Ozer
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  190     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2002 Mar 
Date Detail:
Created Date:  2002-02-21     Completed Date:  2002-03-06     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  332-44     Citation Subset:  IM    
Copyright Information:
Copyright 2002 Wiley-Liss, Inc.
Affiliation:
Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School and Graduate School of Biomedical Sciences, Newark, New Jersey 07103-2714, USA.
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MeSH Terms
Descriptor/Qualifier:
Antigens, Polyomavirus Transforming
Antigens, Viral, Tumor / analysis,  physiology
Apoptosis / physiology*
Caenorhabditis elegans Proteins
Cell Death / physiology*
Cell Line, Transformed
Fibroblasts / physiology*
Humans
Receptors, Tumor Necrosis Factor / physiology
Telomere / physiology
Tumor Suppressor Protein p53
Grant Support
ID/Acronym/Agency:
AG00378/AG/NIA NIH HHS; AG04821/AG/NIA NIH HHS; CA09665/CA/NCI NIH HHS; CA64173/CA/NCI NIH HHS; K11-CA64173/CA/NCI NIH HHS; P01 AG00378/AG/NIA NIH HHS; R01 AG04821/AG/NIA NIH HHS; T32-CA09665/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Polyomavirus Transforming; 0/Antigens, Viral, Tumor; 0/CEP-1 protein, C elegans; 0/Caenorhabditis elegans Proteins; 0/Receptors, Tumor Necrosis Factor; 0/Tumor Suppressor Protein p53

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