Kawamura Kiyoko, Yu Ling, Tomizawa Minoru, Shimozato Osamu, Ma Guangyu, Li Quanhai, Sato Ayako, Yang Yanling, Suzuki Takeo, Abdel-Aziz Nashwa Mohamed, Tagawa Masatoshi
Division of Pathology, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan.
Anticancer Res. 2007 Jan-Feb;27(1A):89-93.
Selective expression of a therapeutic gene in tumors contributes to the efficacy and the safety of cancer therapy. Regulatory regions of genes that are preferentially expressed in tumors have been examined. The regions of the survivin gene exhibited the greatest activity in human hepatocellular carcinoma cells. Deletion of the survivin regulatory region from the 5'-side demonstrated that the 0.5 kb and the 1.4 kb fragments possessed a strong promoter activity with relative tumor specificity. Human tumors transfected with the herpes simplex virus-thymidine kinase gene, that was powered by the survivin region, became susceptible to a prodrug, ganciclovir. Although survivin gene expression was up-regulated in the G2/M-phase of the cell cycle, taxol or vincristine treatment, which induce cell cycle arrest at the M-phase, did not enhance the transcriptional activity of the survivin promoter. These data collectively suggest that the survivin regulatory region induces the expression of an exogenous gene in tumors, but the transcriptional activity is not directly linked with M-phase induction.
治疗性基因在肿瘤中的选择性表达有助于癌症治疗的疗效和安全性。人们已经对在肿瘤中优先表达的基因的调控区域进行了研究。存活素基因的区域在人肝癌细胞中表现出最大活性。从5'端缺失存活素调控区域表明，0.5 kb和1.4 kb片段具有较强的启动子活性和相对肿瘤特异性。用由存活素区域驱动的单纯疱疹病毒胸苷激酶基因转染的人类肿瘤，对前体药物更昔洛韦变得敏感。尽管存活素基因表达在细胞周期的G2/M期上调，但诱导细胞周期停滞在M期的紫杉醇或长春新碱处理并未增强存活素启动子的转录活性。这些数据共同表明，存活素调控区域可诱导肿瘤中外源基因的表达，但转录活性与M期诱导无直接关联。
