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

doi:10.1038/5063

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

Research output: Contribution to journal › Article › peer-review

701 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 language	English (US)
Pages (from-to)	115-118
Number of pages	4
Journal	Nature Genetics
Volume	21
Issue number	1
DOIs	https://doi.org/10.1038/5063
State	Published - Jan 1999
Externally published	Yes

ASJC Scopus subject areas

Genetics

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title = "Absence of cancer-associated changes in human fibroblasts immortalized with telomerase",

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.",

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

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AU - Morales, Carmela P.

AU - Holt, Shawn E.

AU - Ouellette, Michel

AU - Kaur, Kiran J.

AU - Yan, Ying

AU - Wilson, Kathleen S.

AU - White, Michael A.

AU - Wright, Woodring E.

AU - Shay, Jerry W.

PY - 1999/1

Y1 - 1999/1

N2 - 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.

AB - 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.

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

Abstract

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