卵巢癌
生物
癌症研究
癌基因
逆转录病毒
细胞培养
基因表达
胸苷激酶
转基因
基因
更昔洛韦
报告基因
遗传增强
分子生物学
癌症
单纯疱疹病毒
病毒学
病毒
细胞周期
人巨细胞病毒
遗传学
作者
Muthu Selvakumaran,Rudi Bao,Anne P G Crijns,Denise C. Connolly,Jillian K. Weinstein,Thomas A. Hamilton
出处
期刊:PubMed
日期:2001-02-15
卷期号:61 (4): 1291-5
被引量:19
摘要
We have isolated 462 bp of sequence termed ovarian-specific promoter 1 (OSP-1) that is part of a retrovirus-like element specifically expressed in the rat ovary. We have evaluated the ability of OSP-1 to activate gene expression in normal and neoplastic cell lines derived from the ovaries of rats and women. We have found that there was marked specificity in the ability of OSP-1 to drive reporter gene expression in an ovarian epithelial cell lineage manner. The expression of herpes simplex virus thymidine kinase (HSV-TK) under OSP-1 control was sufficiently ovarian cancer cell line specific to render ganciclovir approximately 50-fold more toxic in the A2780 human ovarian cancer cell line compared with clones of the HCT-116 and HT-29 colon cancer cell lines. Furthermore, ganciclovir had marked antitumor efficacy in vivo in severe combined immunodeficient mice bearing A2780OSP-1-HSV-TK as a s.c. xenograft. We suggest that these data support the use of OSP-1 as a tool to provide specificity to the gene therapy of ovarian cancer and to drive ovarian-specific oncogene expression for the creation of transgenic mouse models of ovarian cancer.
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