GSBS Student Publications
Title
Short dysfunctional telomeres impair tumorigenesis in the INK4a(delta2/3) cancer-prone mouse
GSBS Program
Biochemistry & Molecular Pharmacology
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Microbiology and Immunology
Date
5-25-1999
Document Type
Article
Medical Subject Headings
Animals; Antigens, Polyomavirus Transforming; Cell Division; Cell Line, Transformed; Cyclin-Dependent Kinase Inhibitor p16; Mice; Mice, SCID; Neoplasms; Phenotype; Telomerase; Telomere
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.
Rights and Permissions
Citation: Cell. 1999 May 14;97(4):515-25.
Related Resources
Journal Title
Cell
PubMed ID
10338215
Repository Citation
Greenberg, Roger A.; Chin, Lynda; Femino, Andrea M.; Lee, Kee-Ho; Gottlieb, Geoffrey J.; Singer, Robert H.; Greider, Carol W.; and DePinho, Ronald A., "Short dysfunctional telomeres impair tumorigenesis in the INK4a(delta2/3) cancer-prone mouse" (1999). GSBS Student Publications. 412.
https://escholarship.umassmed.edu/gsbs_sp/412