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

为了了解端粒的维持机制，我们测量了端粒酶组分、端粒重复结合因子及其相关蛋白的基因表达。几乎在癌症中发现了端粒酶的活性，但在邻近的正常细胞中没有发现。然而，端粒酶活性与癌细胞端粒长度无关。结果表明，端粒长度可能不是由端粒酶单独调节的。TRF1、TRF2和TIN2是端粒长度的负调控因子，tankyase和Rapl是正调控因子。与非癌组织相比，癌症组织中的TRF1、TRF2和TIN2 rna显著下调。tankyase和Rap1在癌症中均未上调。除了端粒酶的再激活外，TRF1、TRF2和TIN2基因表达的下调可能对逃避癌症端粒长度缩短引起的细胞死亡也很重要。因此，目前hTERT、TRFs和TIN2可能是胰腺癌基因治疗的合适靶点。

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.