Abstract
The ectopic expression of telomerase in normal human cells results in an extended lifespan, indicating that telomere shortening regulates the timing of cellular senescence. As telomerase expression is a hallmark of cancer, we investigated the long-term effects of forced expression of human telomerase catalytic component (hTERT) in normal human fibroblasts. In vitro growth requirements, cell-cycle checkpoints and karyotypic stability in telomerase-expressing cells are similar to those of untransfected controls. In addition, co-expression of telomerase, the viral oncoproteins HPV16 E6/E7 (which inactivate p53 and pRB) and oncogenic HRAS does not result in growth in soft agar. Thus, although ectopic expression of telomerase in human fibroblasts is sufficient for immortalization, it does not result in changes typically associated with malignant transformation.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Catalytic Domain* / genetics
-
Cell Division
-
Cell Line
-
Cellular Senescence*
-
Cyclin-Dependent Kinase Inhibitor p21
-
Cyclins / metabolism
-
DNA-Binding Proteins
-
Fibroblasts / cytology*
-
Galactosidases / biosynthesis
-
Humans
-
Oncogene Proteins, Viral / genetics
-
Papillomavirus E7 Proteins
-
Phosphorylation
-
Proteins / genetics
-
Proteins / metabolism*
-
Proto-Oncogene Proteins p21(ras) / genetics
-
RNA*
-
Repressor Proteins*
-
Retinoblastoma Protein / metabolism
-
Telomerase / genetics
-
Telomerase / metabolism*
-
Tumor Suppressor Protein p53 / metabolism
Substances
-
CDKN1A protein, human
-
Cyclin-Dependent Kinase Inhibitor p21
-
Cyclins
-
DNA-Binding Proteins
-
E6 protein, Human papillomavirus type 16
-
Oncogene Proteins, Viral
-
Papillomavirus E7 Proteins
-
Proteins
-
Repressor Proteins
-
Retinoblastoma Protein
-
Tumor Suppressor Protein p53
-
oncogene protein E7, Human papillomavirus type 16
-
telomerase RNA
-
RNA
-
Telomerase
-
Galactosidases
-
HRAS protein, human
-
Proto-Oncogene Proteins p21(ras)