Clonal variation in phenotype and life span of human embryonic fibroblasts (MRC-5) transduced with the catalytic component of telomerase (hTERT) Journal Article

Authors: Franco, S.; Mackenzie, K. L.; Dias, S.; Alvarez, S.; Rafii, S.; Moore, M. A. S.
Article Title: Clonal variation in phenotype and life span of human embryonic fibroblasts (MRC-5) transduced with the catalytic component of telomerase (hTERT)
Abstract: Expression of telomerase (hTERT) in certain cell types has been shown to extend cellular life span without malignant transformation. We studied the phenotype of 26 telomerase-transduced fibroblast clones (TTFC) generated from a mass culture of hTERT retrovirally transduced MRC-5 cells. About two-thirds of the transduced clones senesced at the expected time or shortly thereafter, despite high levels of expression of telomerase and telomere length maintenance. The remaining one-third of the clones were "immortalized" (followed for over 200 cumulative population doublings). All clones maintained a nontransformed phenotype: contact inhibition, anchorage dependency, lack of tumor formation in nude mice, dose dependency to serum and growth factors, low expression of a matrix metalloproteinase associated with metastatic invasion (MMP-9) and high expression of its inhibitor TIMP-1, and no cytogenetic abnormalities by G-banding. In addition, fibroblast-specific biological parameters, such as colony size, production of collagenase, and response to MMC and gamma radiation were tightly regulated at the clonal and subclonal levels. © 2001 Academic Press.
Keywords: signal transduction; controlled study; protein expression; human cell; dna-binding proteins; dose response; nonhuman; animal cell; mouse; phenotype; telomere; animals; mice; cell survival; cell division; radiation; embryo; gelatinase b; cell line; animal experiment; animal model; genetic variability; cytogenetics; dose-response relationship, drug; telomerase; dose-response relationship, radiation; carcinogenesis; cell type; mus musculus; transduction, genetic; rna; mice, nude; matrix metalloproteinase; transplantation, heterologous; fibroblast; fibroblasts; mitomycin c; cell size; senescence; mitomycin; malignant transformation; colony-forming units assay; growth factor; catalytic domain; karyotyping; collagenase; anchorage independent growth; cell invasion; clone cells; enzyme mechanism; metalloproteinase; lifespan; tissue inhibitor of metalloproteinase 1; embryo cell; enzyme active site; contact inhibition; growth substances; colony formation; cell immortalization; gamma radiation; gamma rays; tissue inhibitor of metalloproteinase-1; gelatinases; immortalization; humans; human; male; priority journal; article; mrc-5
Journal Title: Experimental Cell Research
Volume: 268
Issue: 1
ISSN: 0014-4827
Publisher: Elsevier Inc.  
Date Published: 2001-08-01
Start Page: 14
End Page: 25
Language: English
DOI: 10.1006/excr.2001.5264
PUBMED: 11461114
PROVIDER: scopus
Notes: Export Date: 21 May 2015 -- Source: Scopus
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MSK Authors
  1. Sonia Franco
    12 Franco
  2. Sara Alvarez
    13 Alvarez
  3. Malcolm A S Moore
    446 Moore