Differential regulation of telomerase activity and telomerase RNA during multi-stage tumorigenesis

Blasco, M. A., Rizen, M., Greider, C. W., Hanahan, D. (February 1996) Differential regulation of telomerase activity and telomerase RNA during multi-stage tumorigenesis. Nature Genetics, 12 (2). pp. 200-4. ISSN 1061-4036 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/8563761
DOI: 10.1038/ng0296-200

Abstract

Telomeres consist of short repeated sequences that are synthesized by telomerase, a ribonucleo-protein DNA polymerase. Telomerase activity is present in many tumours and not detected in many normal tissues. Telomere shortening in human and mouse tissues and primary cell cultures may be due to the absence of telomerase activity. To determine when telomerase is activated during tumour development and progression, we examined telomerase activity and expression of the recently cloned mouse telomerase RNA component (mTR) in two different transgenic mouse models of multi-stage tumorigenesis. These mouse models allow examination of many independent tumours from genetically identical individuals. These mice reproducibly develop pancreatic islet cell carcinoma and squamous cell carcinoma of the skin. In both carcinoma types, we detected telomerase activity only in late-stage tumours; in contrast, we found mTR levels were upregulated in the early preneoplastic stages, and further increased during progression. Surprisingly, mTR levels did not parallel the amount of telomerase activity detected and a subset of tumours lacked telomerase activity and yet expressed telomerase RNA. Regulation of telomerase activity may therefore be separable from expression of its RNA component. These results clearly demonstrate telomerase is activated in late stages of tumour progression, and show for the first time that the initial up regulation of telomerase RNA is an early event, concurrent with the hyperproliferation elicited by viral oncogenes.

Item Type: Paper
Uncontrolled Keywords: Animals Carcinoma/ chemistry/ enzymology/pathology Carcinoma, Islet Cell/chemistry/enzymology/pathology Carcinoma, Squamous Cell/chemistry/enzymology/pathology Disease Models, Animal Disease Progression Lymph Nodes/enzymology Mice Mice, Transgenic Pancreatic Neoplasms/chemistry/enzymology/pathology RNA/analysis RNA, Neoplasm/ analysis Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Skin Neoplasms/chemistry/enzymology/pathology Telomerase/ metabolism
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > telomerase
CSHL Authors:
Communities: CSHL labs > Greider lab
Depositing User: Matt Covey
Date: February 1996
Date Deposited: 22 May 2014 19:28
Last Modified: 22 May 2014 19:28
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30144

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