MECHANISM OF REGULATION OF TELOMERASE EXPRESSION, AND EXPERIMENTAL STUDY ON CANCER GENE THERAPY USING ITS PROMOTER.

人类端粒酶逆转录酶（hTERT）是端粒酶的催化亚基，在永生化细胞中高度活跃。我们利用hTERT启动子进行肿瘤基因治疗的基础实验。通过缺失分析鉴定出核心启动子区域，该区域的去甲基化加速了p16和E-cadherin的表达。胞嘧啶脱氨酶基因连接在hTERT启动子下游。体外实验表明，该药物仅对癌细胞有杀伤作用，对正常细胞无杀伤作用。为了在基因治疗中创造更活跃和特异的工具，串联重复启动子正在研究中。构建了含hTERT启动子和CD的腺病毒载体，并进行了体内实验。该数据具有特异性，在肿瘤基因治疗领域具有广阔的应用前景。

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase, which is highly active in immortalized cells. We herein carried out basic experiments on cancer gene therapy utilizing the hTERT promoter. The core promoter region was identified by deletion analysis, and demethylation of this region accelerated the expression of p16 and E-cadherin. Cytosine deaminase gene was ligated in downstream of hTERT promoter. In vitro experiments demonstrated that cell- kill effect was only seen in cancer cells not in normal cells. Tandem repeat promoter is now under construction for creating more active and specific tool in gene therapy. Adenovirus vector containing hTERT promoter and CD was constructed, and used in vivo experiments. The data was promising and could be widely utilized in the field of cancer gene therapy because of its specificity.