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 language | English (US) |
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Pages (from-to) | 14-25 |
Number of pages | 12 |
Journal | Experimental cell research |
Volume | 268 |
Issue number | 1 |
DOIs | |
State | Published - Aug 1 2001 |
Externally published | Yes |
Keywords
- Immortalization
- MRC-5
- Metalloproteinase
- Mitomycin C
- Radiation
- Senescence
- Telomerase
- Telomere
ASJC Scopus subject areas
- Cell Biology