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

Link to article in PubMed

Journal Title

Cell

PubMed ID

10338215