Reversible downregulation of telomerase activity by hyperthermia in osteosarcoma cells

Telomerase, a ribonucleoprotein enzyme, maintains telomere length and is ex pressed by the majority of malignant tumours, but not in normal tissue. Tel omerase facilitates the division of tumour cells and its activity has been suggested as a prognostic indicator, but so far the regulation or modulatio n of telomerase activity has not been described. Hyperthermia has been show n to decrease tumour growth by inhibition of proliferation. Therefore, the effect of hyperthermia on telomerase activity in human osteosarcoma cells w as studied. Telomerase activity was measured by the Telomeric Repeat Amplif ication Protocol (TRAP) assay in three different osteosarcoma cell lines su bjected to hyperthermia (42.5 degrees C, 90 min) and in controls cultured u nder basal conditions (37 degrees C). Telomerase activity was strongly inhi bited by hyperthermia and decreased in all cell lines tested after a recove ry time of 2 h under basal conditions (37 degrees C) to an activity of simi lar to 85%, after 12 h similar to 60% and with lowest activity similar to 5 5% compared to activity of control cells. Telomearase activity then increas ed and reached the same, i.e. basal, level as before hyperthermia, after 11 2 h. These results show that hyperthermia results in a reversible downregul ation of telomerase activity in osteosarcoma cells. This effect facilities studies on the regulation of telomerase activity and detailed information m ight lead to new therapeutic strategies.