Ultraviolet irradiation- and dimethyl sulfoxide-induced telomerase activity in ovarian epithelial cell lines.
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.
Alfonso-De Matte
M Y
MY
H. Lee Moffitt Cancer Center, University of South Florida, Tampa, Florida 33612, USA.
Cheng
J Q
JQ
Kruk
P A
PA
D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004847:Epithelial Cells / Q000201:enzymology* / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology; D010053:Ovary / Q000201:enzymology* / Q000473:pathology; D019098:Telomerase / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D019098:Telomerase; D004121:Dimethyl Sulfoxide