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 main tains telomere length, may be essential for unlimited cell proliferati on irt vivo and in vitro. Telomerase is not expressed in most human so matic cells but is a nearly ubiquitous tumour marker, being activated in malignant cells from many cancers, Inhibition of telomerase may lea d to telomere shortening and eventually limit the proliferative capaci ty of malignant cells and hence be of therapeutic value, With the inte nt of characterizing an animal model for inhibition studies, we invest igated telomerase activity during mammary tumorigenesis in transgenic mice overexpressing the neu gene, We detected activity in primary mamm ary tumours and lung metastases but also in normal mammary glands and other organs, Activity Tvas elevated in tumors versus normal tissues a nd was enhanced by short-term culturing of normal cells, Telomerase ac tivity was also present in somatic tissues from the non-transgenic par ental strain and the outbred Mus spretus strain, As we recently detect ed telomerase activity in normal human hemopoietic tissues, mouse mode ls of tumorigenesis may provide useful experimental systems for assess ing the outcome of in vivo inhibition of telomerase in both malignant and normal cells.