Regulation of telomerase activity in quiescent immortalized human cells.

Telomerase is a key enzyme in carcinogenesis; telomerase activity has been found in more than 90% of human tumors. Understanding the regulation of this enzyme will improve our knowledge of tumor biology and may lead to novel strategies in cancer therapy. We examined effects of growth arrest on telomerase activity in the human immortalized cell lines U 937 (lymphoma) and L 428 (Hodgkin's disease). Cells were starved by serum depletion for 4 days. After readdition of serum, a recovery phase followed. Cell proliferation was monitored with the monoclonal antibody Ki-S5. In the absence of serum, telomerase levels declined fivefold. After serum readdition, recovery to threefold increased level was observed. Furthermore, the prevalence of telomerase-positive cells in normal tissues is an important issue for understanding tumorigenesis. Our TRAP assay is robust against false positives and in mixed cell samples, we found a rather limited sensitivity of the telomere repeat amplification protocol (TRAP) assay. This means that adequate screenings for telomerase-positive somatic cells have to include enrichment steps.