Telomerase activity in normal and malignant murine tissues.
Telomere shortening may contribute to the limited lifespan of somatic cells and telomerase, the enzyme that elongates telomeric DNA and maintains telomere length, may be essential for unlimited cell proliferation in vivo and in vitro. Telomerase is not expressed in most human somatic cells but is a nearly ubiquitous tumour marker, being activated in malignant cells from many cancers. Inhibition of telomerase may lead to telomere shortening and eventually limit the proliferative capacity of malignant cells and hence be of therapeutic value. With the intent of characterizing an animal model for inhibition studies, we investigated telomerase activity during mammary tumorigenesis in transgenic mice overexpressing the neu gene. We detected activity in primary mammary tumours and lung metastases but also in normal mammary glands and other organs. Activity was elevated in tumors versus normal tissues and was enhanced by short-term culturing of normal cells. Telomerase activity was also present in somatic tissues from the non-transgenic parental strain and the outbred Mus spretus strain. As we recently detected telomerase activity in normal human hemopoietic tissues, mouse models of tumorigenesis may provide useful experimental systems for assessing the outcome of in vivo inhibition of telomerase in both malignant and normal cells.
Chadeneau
C
C
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Siegel
P
P
Harley
C B
CB
Muller
W J
WJ
Bacchetti
S
S
D000818:Animals; D004253:DNA Nucleotidylexotransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D018734:Genes, erbB-2; D008321:Mammary Glands, Animal / Q000201:enzymology; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology* / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D014407:Tumor Cells, Cultured
D004253:DNA Nucleotidylexotransferase