Immortalized mouse mammary cells in vivo do not exhibit increased telomerase activity

The acquisition of immortalization is an early and carefully documented event in mouse mammary tumorigenesis. Activation of telomerase activity is one hypothesis to explain the acquisition of immortalization. We examined the activity of telomerase in well-defined immortalized, non- tumor cell populations of mouse mammary tissue in vivo. The results indicated that normal virgin and mid-pregnant mammary gland had low to moderate levels of telomerase activity, respectively. In comparison with the levels detected in pregnant mammary gland, telomerase activity was elevated in mammary tumors in situ and in established mammary cell lines in vitro, both tumorigenic and nontumorigenic; however, hyperplastic alveolar preneoplastic mammary outgrowths and non- tumorigenic ductal outgrowths, both in vivo immortalized populations, had telomerase activity <12% of the levels detected in normal pregnant mammary gland. These results suggest that elevated telomerase activity is not necessary for the immortalization phenotype in in vivo mouse mammary cell populations and that elevated telomerase activity occurs as a late event in mammary tumorigenesis. Furthermore, the data suggest that low levels of telomerase activity are characteristic for mouse mammary epithelial cells and not sufficient for immortalization. These data suggest that other factors play more important roles in the induction and/or maintenance of the immortalization state in mammary cell populations.