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

Sonia Franco, K. L. MacKenzie, S. Dias, S. Alvarez, S. Rafii, M. A S Moore

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)14-25
Number of pages12
JournalExperimental Cell Research
Volume268
Issue number1
DOIs
StatePublished - Aug 1 2001

Fingerprint

Telomerase
Clone Cells
Fibroblasts
Phenotype
Matrix Metalloproteinases
Telomere Homeostasis
Contact Inhibition
Tissue Inhibitor of Metalloproteinase-1
Gamma Rays
Collagenases
Nude Mice
Chromosome Aberrations
Intercellular Signaling Peptides and Proteins
Serum
Population
Neoplasms

Keywords

  • Immortalization
  • Metalloproteinase
  • Mitomycin C
  • MRC-5
  • Radiation
  • Senescence
  • Telomerase
  • Telomere

ASJC Scopus subject areas

  • Cell Biology

Cite this

Clonal variation in phenotype and life span of human embryonic fibroblasts (MRC-5) transduced with the catalytic component of telomerase (hTERT). / Franco, Sonia; MacKenzie, K. L.; Dias, S.; Alvarez, S.; Rafii, S.; Moore, M. A S.

In: Experimental Cell Research, Vol. 268, No. 1, 01.08.2001, p. 14-25.

Research output: Contribution to journalArticle

Franco, Sonia ; MacKenzie, K. L. ; Dias, S. ; Alvarez, S. ; Rafii, S. ; Moore, M. A S. / Clonal variation in phenotype and life span of human embryonic fibroblasts (MRC-5) transduced with the catalytic component of telomerase (hTERT). In: Experimental Cell Research. 2001 ; Vol. 268, No. 1. pp. 14-25.
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