Transcriptional Up-Regulation of Tert and Terc Necessarily Not Mean Higher Telomerase Activity: A Report of Telomerase Inhibition with Higher Transcription of Tert, Terc and Terf2 in A549 Cells Treated with Staurosporine
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Ratan Sadhukhan, and Utpal Ghosh*
Targeting telomerase is one of the approaches to kill cancer cells since almost 90% cancer are telomerase-positive. TERT and TERC are essential subunits of telomerase and a number of reports available regarding telomerase inhibitions due to inhibition of either of the essential subunits. Here, we present inhibition of telomerase activity with up-regulation of TERT and TERC in A549 cells treated with staurosporin, a potent protein kinase inhibitor. Staurosporin was known to inhibit telomerase and we also observed time-dependent telomerase inhibition by staurosporin. Notably, staurosporin up-regulates the transcription of TERT and TERC with time. This data implicates higher expression of TERT and TERC does not enhance telomerase activity always and there must be other post-transcriptional factors that regulate telomerase activity. Furthermore, staurosporine enhances TERF2 expression in a time-dependent manner implicating that it may alter native telomere structure. Staurosporine induced apoptosis is well-established fact. Here, we compared staurosporine induced telomerase inhibition and apoptosis induction in a time frame to elucidate whether these two events are independent or not in our case. We observed that significant apoptosis induction (12h) was earlier event than significant telomerase inhibition (24h) after staurosporine treatment. Our data suggests, staurosporine transcriptionally elevates TERT and TERC but reduces telomerase activity and may alter telomere native structure via up-regulation of TERF2. Higher transcription of essential subunits of telomerase does not assure higher telomerase activity. Since induction of apoptosis is earlier event than telomerase inhibition, staurosporine induces apoptosis independent of telomerase inhibition.