Title
Short dysfunctional telomeres impair tumorigenesis in the INK4a(delta2/3) cancer-prone mouse
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Microbiology and Immunology
Publication Date
1999-05-25
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
Maintenance of telomere length is predicted to be essential for bypass of senescence and crisis checkpoints in cancer cells. The impact of telomere dysfunction on tumorigenesis was assessed in successive generations of mice doubly null for the telomerase RNA (mTR) and the INK4a tumor suppressor genes. Significant reductions in tumor formation in vivo and oncogenic potential in vitro were observed in late generations of telomerase deficiency, coincident with severe telomere shortening and associated dysfunction. Reintroduction of mTR into cells significantly restored the oncogenic potential, indicating telomerase activation is a cooperating event in the malignant transformation of cells containing critically short telomeres. The results described here demonstrate that loss of telomere function in a cancer-prone mouse model possessing intact DNA damage responses impairs, but does not prevent, tumor formation.
DOI of Published Version
10.1016/S0092-8674(00)80761-8
Source
Cell. 1999 May 14;97(4):515-25.
Journal/Book/Conference Title
Cell
Related Resources
PubMed ID
10338215
Repository Citation
Greenberg RA, Chin L, Femino AM, Lee K, Gottlieb GJ, Singer RH, Greider CW, DePinho RA. (1999). Short dysfunctional telomeres impair tumorigenesis in the INK4a(delta2/3) cancer-prone mouse. GSBS Student Publications. https://doi.org/10.1016/S0092-8674(00)80761-8. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/412