Ultraviolet irradiation- and dimethyl sulfoxide-induced telomerase activity in ovarian epithelial cell lines

Information about telomerase regulation is incomplete, especially since var ious studies suggest complexity in telomerase regulation. Given the importa nt association between telomerase and cancer, it is imperative to design an d develop a model system in which telomerase activity can be regulated and studied. We employed ultraviolet (UV radiation or dimethyl sulfoxide (DMSO) to transiently induce telomerase activity in a telomerase-positive cell li ne and, most importantly, in a telomerase-negative cell line. UV- or DMSO-i nduced telomerase activity was associated with increased hTRT, but not hTR, mRNA transcription in the telomerase-negative cells. However, no changes i n hTRT or hTR mRNA transcription were noted with UV- or DMSO-induced telome rase activity in the telomerase-positive cells. Inhibition of protein synth esis or the phosphotidyl inositol 3-kinase (PI3K) pathway suppressed telome rase induction and/or activity in all cell lines examined, suggesting telom erase activity was dependent on protein synthesis and PI3K-mediated phospho rylation. Furthermore, enhanced telomerase activity was limited to UV and D MSO, since a variety of chemotherapeutic agents failed to induce telomerase activity. Therefore, our data provide a useful culture model system to stu dy telomerase regulation in telomerase-negative and -positive cell lines an d from which to obtain information about telomerase as a target for cancer intervention. (C) 2001 Academic Press.