Document Detail

Spontaneous immortalization of clinically normal colon-derived fibroblasts from a familial adenomatous polyposis patient.
MedLine Citation:
PMID:  15153338     Owner:  NLM     Status:  MEDLINE    
Normal human diploid cells do not spontaneously immortalize in culture, but instead enter replicative senescence after a finite number of population doublings. Ablation of key checkpoint arrest or cancer-suppressor genes, through dominantly inherited germline mutation (p53+/-, Li-Fraumeni) or viral oncogene expression (SV40 large T, HPV16/18, and E6/E7) can lead to escape from senescence, additional doublings, and entrance into crisis phase, where immortal clones emerge at low frequency. In the vast majority of cases, telomerase is reactivated and telomeres are stabilized. Here we describe the spontaneous immortalization of clinically normal fibroblasts derived from colonic stroma of a familial adenomatous polyposis (FAP) patient. The preimmortal (C26C) and the spontaneously immortalized derivative (C26Ci) cells are heterozygous for a characterized germline mutation in exon 15 of the adenomatous polyposis coli gene. Immortalization was accompanied by spontaneous reactivation of endogenous telomerase and establishment of telomeres at presenescent lengths. Normal checkpoint behavior is retained and a diploid karyotype is maintained. These cells provide a valuable new addition to the limited number of spontaneously immortalized human cell types, particularly fibroblast cells, and will be useful in experimentally determining the functional pathways in neoplastic development and in the identification of potential molecular targets for cancer chemoprevention.
Nicholas R Forsyth; Carmela P Morales; Shirish Damle; Bruce Boman; Woodring E Wright; Levy Kopelovich; Jerry W Shay
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neoplasia (New York, N.Y.)     Volume:  6     ISSN:  1522-8002     ISO Abbreviation:  Neoplasia     Publication Date:    2004 May-Jun
Date Detail:
Created Date:  2004-05-21     Completed Date:  2004-12-10     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  100886622     Medline TA:  Neoplasia     Country:  United States    
Other Details:
Languages:  eng     Pagination:  258-65     Citation Subset:  IM    
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
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MeSH Terms
Adenomatous Polyposis Coli / genetics,  pathology*
Cell Line, Transformed
Cell Nucleus / metabolism
Cell Proliferation
Colon / cytology*
Cytoskeletal Proteins / metabolism
DNA Damage
Fibroblasts / enzymology,  metabolism,  pathology*
Genes, APC
Oxidative Stress
Telomerase / metabolism
Telomere / metabolism
Trans-Activators / metabolism
beta Catenin
Grant Support
Reg. No./Substance:
0/CTNNB1 protein, human; 0/Cytoskeletal Proteins; 0/Trans-Activators; 0/beta Catenin; EC

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