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

Carmela P. Morales, Shawn E. Holt, Michel Ouellette, Kiran J. Kaur, Ying Yan, Kathleen S. Wilson, Michael A. White, Woodring E. Wright, Jerry W. Shay

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654 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)115-118
Number of pages4
JournalNature Genetics
Volume21
Issue number1
DOIs
StatePublished - Jan 1999

ASJC Scopus subject areas

  • Genetics

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    Morales, C. P., Holt, S. E., Ouellette, M., Kaur, K. J., Yan, Y., Wilson, K. S., White, M. A., Wright, W. E., & Shay, J. W. (1999). Absence of cancer-associated changes in human fibroblasts immortalized with telomerase. Nature Genetics, 21(1), 115-118. https://doi.org/10.1038/5063