A novel mechanism for chaperone-mediated telomerase regulation during prostate cancer progression

Telomerase activity has been detected in > 85 % of all malignant human canc ers, including 90% of prostate carcinomas. Using a well-characterized exper imental prostate cancer system, we have found that telomerase activity is n otably increased (> 10-fold) during tumorigenic conversion. Expression prof iles of the telomerase components (hTR and hTERT) revealed no substantive c hanges, which suggests a nontranscriptional mechanism for increased activit y. Because the hsp90 chaperone complex functionally associates with telomer ase, we investigated that relationship and found that along with telomerase activity, a number of hsp90-related chaperones are markedly elevated durin g transformation, as well as in advanced prostate carcinomas. Using the non tumorigenic cell protein extract as the source of telomerase, addition of p urified chaperone components enhanced reconstitution of telomerase activity , which suggests a novel mechanism of increased telomerase assembly via a h sp90 chaperoning process during prostate cancer progression.