TELOMERASE ACTIVITY IN HUMAN OVARIAN-CARCINOMA

Telomeres fulfill the dual function of protecting eukaryotic chromosom es from illegitimate recombination and degradation and may aid in chro mosome attachment to the nuclear membrane. We have previously shown th at telomerase, the enzyme which synthesizes telomeric DNA, is not dete cted in normal somatic cells and that telomeres shorten with replicati ve age. In cells immortalized in vitro, activation of telomerase appar ently stabilizes telomere length, preventing a critical destabilizatio n of chromosomes, and cell proliferation continues even when telomeres are short. In vivo, telomeres of most tumors are shorter than telomer es of control tissues, suggesting an analogous role for the enzyme. To assess the relevance of telomerase and telomere stability in the deve lopment and progression of tumors, we have measured enzyme activity an d telomere length in metastatic cells of epithelial ovarian carcinoma. We report that extremely short telomeres are maintained in these cell s and that tumor cells, but not isogenic nonmalignant cells, express t elomerase. Our findings suggest that progression of malignancy is ulti mately dependent upon activation of telomerase and that telomerase inh ibitors may be effective antitumor drugs.