Establishment of gene therapy for panceratic cancer, targeting genes for the components of telomerase and telomeric-repeat binding proteins.

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To understand the mechanism for maintenance of telomeres, we performed measurement for gene expression for telomerase components, and telomeric-repeat binding factor and its associated protein. Telomerase activity has been found in almost cancers but not in adjacent normal cells. However, telomerase activity did not correlate with telomere length in cancer cells. The results suggest that telomere length may not be regulated by telomerase alone. TRF1, TRF2, and TIN2 are negative regulators of telomere length, and tankyrase and Rapl act as positive regulators. TRF1, TRF2, and TIN2 RNAs were significantly down-regulated in cancers compared to noncancerous tissues. Neither tankyrase nor Rap1 was up-regulated in cancers.In addition to reactivation of telomerase, down-regulation of TRF1, TRF2, and TIN2 gene expression may be important to escape from the cell death caused by shortening telomere length in cancers. At present time, therefore hTERT, TRFs and TIN2 may be suitable targets for gene therapy for pancreatic cancer.