Telomere shortening and tumor formation by mouse cells lacking telomerase RNA

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)

URL: http://www.ncbi.nlm.nih.gov/pubmed/9335332
DOI: 10.1016/S0092-8674(01)80006-4

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: http://repository.cshl.edu/id/eprint/30015

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