@article{eaff41541d9545e6801af3583675369b,
title = "Short dysfunctional telomeres impair tumorigenesis in the INK4a(Δ2/3) cancer-prone mouse",
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.",
author = "Greenberg, {Roger A.} and Lynda Chin and Andrea Femino and Lee Kee-Ho and Gottlieb, {Geoffrey J.} and Singer, {Robert H.} and Greider, {Carol W.} and DePinho, {Ronald A.}",
note = "Funding Information: We thank members of the DePinho lab, particularly Ned Sharpless, for critical reading of the manuscript, Shailish Shenoy for expert advice on imaging and analysis of Q-FISH samples, and Lynn Emerson for outstanding administrative assistance. We are most grateful to the expert histological technical support from B. Furman, K. E. Cedeno-Baier, and L. Husted. This work was supported by grants from the National Institutes of Health (HD348880 and HD28317) and AHA grant-in-aid to R. A. D. NIH support to C. W. G. (CA16519) and to R. S. and A. F. (GM54887) is acknowledged. L. C. is supported by an NIH Mentored Clinician Scientist Award KO8AR02104. R. A. G. is supported by an NIH Training Grant 5T32GM07491. This work was done in partial fulfillment for the Ph.D. requirement for R. A. G.; R. A. D. is an American Cancer Society Research Professor. Support from the DFCI Cancer Core grant to R. A. D. and L. C. is acknowledged. ",
year = "1999",
month = may,
day = "14",
doi = "10.1016/S0092-8674(00)80761-8",
language = "English (US)",
volume = "97",
pages = "515--525",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}