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 regulat ion of this enzyme will improve our knowledge of tumor biology and may lead to novel strategies in cancer therapy. We examined effects of gr owth arrest on telomerase activity in the human immortalized cell line s U 937 (lymphoma) and L 428 (Hodgkin's disease). Cells were starved b y serum depletion for 4 days. After readdition of serum, a recovery ph ase followed. Cell proliferation was monitored with the monoclonal ant ibody Ki-SS, In the absence of serum, telomerase levels declined fivef old. 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 sa mples, we found a rather limited sensitivity of the telomere repeat am plification protocol (TRAP) assay. This means that adequate screenings for telomerase-positive somatic cells have to include enrichment step s. (C) 1998 Elsevier Science B.V. All rights reserved.