Information about telomerase regulation is incomplete, especially since various studies suggest complexity in telomerase regulation. Given the important association between telomerase and cancer, it is imperative to design and 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 line and, most importantly, in a telomerase-negative cell line. UV- or DMSO-induced telomerase activity was associated with increased hTRT, but not hTR, mRNA transcription in the telomerase-negative cells. However, no changes in hTRT or hTR mRNA transcription were noted with UV- or DMSO-induced telomerase activity in the telomerase-positive cells. Inhibition of protein synthesis or the phosphotidyl inositol 3-kinase (PI3K) pathway suppressed telomerase induction and/or activity in all cell lines examined, suggesting telomerase activity was dependent on protein synthesis and PI3K-mediated phosphorylation. Furthermore, enhanced telomerase activity was limited to UV and DMSO, since a variety of chemotherapeutic agents failed to induce telomerase activity. Therefore, our data provide a useful culture model system to study telomerase regulation in telomerase-negative and -positive cell lines and from which to obtain information about telomerase as a target for cancer intervention.
Copyright 2001 Academic Press.