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

为了了解端粒维持的机制，我们对端粒酶组分、端粒重复序列结合因子及其相关蛋白的基因表达进行了测量。端粒酶活性在大多数癌细胞中均有表达，但在癌旁正常细胞中未见表达。然而，端粒酶活性与癌细胞中端粒长度无关。结果表明，端粒长度可能不是由端粒酶单独调节。TRF1、TRF2和TIN 2是端粒长度的负调节因子，端锚聚合酶和Rap1起正调节因子的作用。与非癌组织相比，TRF1、TRF2和TIN 2 RNA在癌症中显著下调。除了端粒酶的重新激活外，TRF1、TRF2和TIN 2基因表达的下调可能对避免癌症中端粒长度缩短引起的细胞死亡很重要。因此，hTERT、TRFs和TIN 2可能是目前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.