Enhanced suicide gene therapy by chimeric tumor-specific promoter based on HSF1 transcriptional regulation

	Enhanced suicide gene therapy by chimeric tumor-specific promoter based on HSF1 transcriptional regulation
	Wang, JH; Yao, MZ; Zhang, ZL; Gu, JF; Zhang, YH; Li, BH; Sun, LY; Liu, XY
刊名	FEBS LETTERS
	2003
卷号	546 期号:1 页码:315-320
关键词	telomerase reverse transcriptase heat shock factor cytosine deaminase tumor-specific promoter heat shock protein 70 Fas
通讯作者	Liu, XY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,
英文摘要	Two tandem cassettes, one containing the telomerase reverse transcriptase gene (hTERT) promoter upstream of a constitutively activated form of heat shock transcription factor 1 (cHSF1) and followed by the other containing the heat shock protein 70B (hsp70B) promoter (HSE) upstream of the cytosine deaminase (CD) gene, could greatly enhance the efficiency of CD gene therapy while retaining tumor specificity in vitro and in vivo. This hTERT-cHSF1/HSE promoter could restrict gene expression in tumor cells and was about 1.5-3-fold more potent than the cytomegalovirus (CMV) promoter. hTERT-cHSF1/ HSE-CD transfection led to tumor cells more sensitive to 5-fluorocytosine compared with hTERT-CD and its toxicity was comparable to that of CMV-CD. Besides enhancement of promoter activity, cHSF1 overexpression itself could enhance the bystander effect of CD gene therapy that could be reversed by anti-Fas antibody. This system also led to activation of stress-related genes such as hsp70 in tumor cells, which in the presence of cell killing by the cytotoxic gene is a highly immunostimulatory event. Furthermore, a more potent anti-tumor effect of hTERT-cHSF1/HSE-CD was observed in nude mice inoculated with Bcap37 cells. No obvious activity of the hTERT-cHSF1/ HSE promoter was observed in normal tissues after intravenous administration. These results indicate that the hTERT-cHSF1/ HSE promoter is highly tumor-specific and strong with potential application in targeted gene therapy, and therefore may be useful for construction of vectors for systemic therapy. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
学科主题	Biochemistry & Molecular Biology; Biophysics; Cell Biology
类目[WOS]	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
关键词[WOS]	HEAT-SHOCK-PROTEIN ; CYTOSINE DEAMINASE GENE ; EXPRESSION IN-VIVO ; TRANSGENE EXPRESSION ; CANCER ; CELLS ; OVEREXPRESSION ; 5-FLUOROURACIL ; CARCINOMA ; SYSTEM
收录类别	SCI
语种	英语
WOS记录号	WOS:000183964000027
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2400]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Wang, JH,Yao, MZ,Zhang, ZL,et al. Enhanced suicide gene therapy by chimeric tumor-specific promoter based on HSF1 transcriptional regulation[J]. FEBS LETTERS,2003,546(1):315-320.
APA	Wang, JH.,Yao, MZ.,Zhang, ZL.,Gu, JF.,Zhang, YH.,...&Liu, XY.(2003).Enhanced suicide gene therapy by chimeric tumor-specific promoter based on HSF1 transcriptional regulation.FEBS LETTERS,546(1),315-320.
MLA	Wang, JH,et al."Enhanced suicide gene therapy by chimeric tumor-specific promoter based on HSF1 transcriptional regulation".FEBS LETTERS 546.1(2003):315-320.