Blasco, M. A., Lee, H. W., Hande, M. P., Samper, E., Lansdorp, P. M., DePinho, R. A., Greider, C. W.
(October 1997)
Telomere shortening and tumor formation by mouse cells lacking telomerase RNA.
Cell, 91 (1).
pp. 25-34.
ISSN 0092-8674 (Print)
Abstract
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.
| Item Type: |
Paper
|
| Uncontrolled Keywords: |
Aneuploidy
Animals
Cell Survival
Cell Transformation, Neoplastic
Cells, Cultured
Chromosome Aberrations
DNA, Neoplasm/metabolism
Fibroblasts
Mice
Mice, Knockout
Mice, Nude
Neoplasms, Experimental/ pathology
Organ Specificity
RNA/genetics/ physiology
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Telomerase/genetics/ physiology
Telomere/ metabolism |
| Subjects: |
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders > neoplasms
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosome
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function > chromosome
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > telomerase |
| CSHL Authors: |
|
| Communities: |
CSHL labs |
| Depositing User: |
Kathleen Darby
|
| Date: |
3 October 1997 |
| Date Deposited: |
07 May 2014 16:16 |
| Last Modified: |
07 May 2014 16:16 |
| Related URLs: |
|
| URI: |
https://repository.cshl.edu/id/eprint/30015 |
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