Aneuploidy and telomere attrition are independent determinants of crisis in SV40-transformed epithelial cells

Mihaela Velicescu, Jiamei Yu, Brittney-Shea Herbert, Jerry W. Shay, Eileen Granada, Louis Dubeau

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Replicative immortality is achieved in vitro by overcoming two mortality checkpoints, M1 (senescence) and M2 (crisis). Cancer cells are thought to overcome M2 by activating telomerase, an enzyme believed to confer genomic stability in addition to maintaining telomeric sequences above a critical length. Here we show that a subset of cultured ovarian cystadenoma cells expressing SV40 large T-antigen, which allows bypassing of M1, develop a specific type of genomic instability, characterized by numerical (as opposed to structural) chromosomal alterations, that leads to non-telomere-based premature growth arrest/crisis. Cells recover from this type of growth arrest and stabilize their ploidy status without telomerase expression. In these cases, telomeres continue to shorten until a second, telomere-based growth arrest/crisis event is reached. Transfection of the catalytic subunit of telomerase does not immortalize cells harboring severe abnormalities in their DNA ploidy but results in immortalization of diploid cells. We conclude that changes in DNA ploidy constitute an important determinant of growth arrest that is independent of telomere attrition in a subset of SV40 large T-antigen-expressing cystadenoma cells. Reestablishment or emergence of ploidy stability, which is not always dependent on telomerase activation, is necessary for acquisition of the potential to achieve replicative immortality.

Original languageEnglish (US)
Pages (from-to)5813-5820
Number of pages8
JournalCancer Research
Volume63
Issue number18
StatePublished - Sep 15 2003
Externally publishedYes

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Telomere
Aneuploidy
Ploidies
Telomerase
Epithelial Cells
Cystadenoma
Polyomavirus Transforming Antigens
Genomic Instability
Viral Tumor Antigens
Growth
DNA
Diploidy
Transfection
Mortality
Enzymes
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Velicescu, M., Yu, J., Herbert, B-S., Shay, J. W., Granada, E., & Dubeau, L. (2003). Aneuploidy and telomere attrition are independent determinants of crisis in SV40-transformed epithelial cells. Cancer Research, 63(18), 5813-5820.

Aneuploidy and telomere attrition are independent determinants of crisis in SV40-transformed epithelial cells. / Velicescu, Mihaela; Yu, Jiamei; Herbert, Brittney-Shea; Shay, Jerry W.; Granada, Eileen; Dubeau, Louis.

In: Cancer Research, Vol. 63, No. 18, 15.09.2003, p. 5813-5820.

Research output: Contribution to journalArticle

Velicescu, M, Yu, J, Herbert, B-S, Shay, JW, Granada, E & Dubeau, L 2003, 'Aneuploidy and telomere attrition are independent determinants of crisis in SV40-transformed epithelial cells', Cancer Research, vol. 63, no. 18, pp. 5813-5820.
Velicescu, Mihaela ; Yu, Jiamei ; Herbert, Brittney-Shea ; Shay, Jerry W. ; Granada, Eileen ; Dubeau, Louis. / Aneuploidy and telomere attrition are independent determinants of crisis in SV40-transformed epithelial cells. In: Cancer Research. 2003 ; Vol. 63, No. 18. pp. 5813-5820.
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