Telomere shortening and tumor formation by mouse cells lacking telomerase RNA.
To examine the role of telomerase in normal and neoplastic growth, the telomerase RNA component (mTR) was deleted from the mouse germline. mTR-/- mice lacked detectable telomerase activity yet were viable for the six generations analyzed. Telomerase-deficient cells could be immortalized in culture, transformed by viral oncogenes, and generated tumors in nude mice following transformation. Telomeres were shown to shorten at a rate of 4.8+/-2.4 kb per mTR-/- generation. Cells from the fourth mTR-/- generation onward possessed chromosome ends lacking detectable telomere repeats, aneuploidy, and chromosomal abnormalities, including end-to-end fusions. These results indicate that telomerase is essential for telomere length maintenance but is not required for establishment of cell lines, oncogenic transformation, or tumor formation in mice.
Pubmed ID: 9335332
- Blasco MA
- Lee HW
- Hande MP
- Samper E
- Lansdorp PM
- DePinho RA
- Greider CW
October 3, 1997
- Agency: NCI NIH HHS, Id: 5P30-CA45508
- Agency: NIA NIH HHS, Id: R01AG09383
- Agency: NICHD NIH HHS, Id: R01HD348880
- Cell Survival
- Cell Transformation, Neoplastic
- Cells, Cultured
- Chromosome Aberrations
- DNA, Neoplasm
- Mice, Knockout
- Mice, Nude
- Neoplasms, Experimental
- Organ Specificity
- Aplastic anemia is related to genes TERC, TRC3, TR, DKCA1, PFBMFT2 which are autosomal dominant according to the OMIM database.
- Pulmonary fibrosis, idiopathic, susceptibility to is related to genes TERC, TRC3, TR, DKCA1, PFBMFT2 which are autosomal dominant according to the OMIM database.
- Dyskeratosis congenita, autosomal dominant 1 is related to genes TERC, TRC3, TR, DKCA1, PFBMFT2 which are autosomal dominant according to the OMIM database.