Absence of telomerase and shortened telomeres have minimal effects on skin and pancreatic carcinogenesis elicited by viral oncogenes

David Argilla, Koei Chin, Mallika Singh, J. Graeme Hodgson, Marcus Bosenberg, Carlos Ortiz De Solórzano, Stephen Lockett, Ronald A. DePinho, Joe Gray, Douglas Hanahan

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The telomere-stabilizing enzyme telomerase is induced in tumors and functionally associated with unlimited replicative potential. To further explore its necessity, transgenic mice expressing SV40 or HPV16 oncogenes, which elicit carcinomas in pancreas and skin, respectively, were rendered telomerase-deficient. Absence of telomerase had minimal impact on tumorigenesis, even in terc-/- generations (G5-7) exhibiting shortened telomeres and phenotypic abnormalities in multiple organs. Analyses of chromosomal aberrations were not indicative of telomere dysfunction or increased genomic instability in tumors. Quantitative image analysis of telomere repeat intensities comparing biopsies of skin hyperplasia, dysplasia, and carcinoma revealed that telomere numbers and relative lengths were maintained during progression, implicating a means for preserving telomere repeats and functionality in the absence of telomerase.

Original languageEnglish (US)
Pages (from-to)373-385
Number of pages13
JournalCancer Cell
Volume6
Issue number4
DOIs
StatePublished - Oct 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Argilla, D., Chin, K., Singh, M., Hodgson, J. G., Bosenberg, M., De Solórzano, C. O., Lockett, S., DePinho, R. A., Gray, J., & Hanahan, D. (2004). Absence of telomerase and shortened telomeres have minimal effects on skin and pancreatic carcinogenesis elicited by viral oncogenes. Cancer Cell, 6(4), 373-385. https://doi.org/10.1016/j.ccr.2004.08.032