Absence of cancer–associated changes in human fibroblasts immortalized with telomerase

CP Morales, SE Holt, M Ouellette, KJ Kaur, Y Yan… - Nature …, 1999 - nature.com
CP Morales, SE Holt, M Ouellette, KJ Kaur, Y Yan, KS Wilson, MA White, WE Wright…
Nature genetics, 1999nature.com
The ectopic expression of telomerase 1, 2 in normal human cells results in an extended
lifespan 3, 4, 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 …
Abstract
The ectopic expression of telomerase 1, 2 in normal human cells results in an extended lifespan 3, 4, 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.
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