Cancer-specific killing by the CD suicide gene using the human telomerase reverse transcriptase promoter

	Cancer-specific killing by the CD suicide gene using the human telomerase reverse transcriptase promoter
	Liu, J; Zou, WG; Lang, MF; Luo, J; Sun, LY; Wang, XN; Qian, QJ; Liu, XY
刊名	INTERNATIONAL JOURNAL OF ONCOLOGY
	2002
卷号	21 期号:3 页码:661-666
关键词	hTERT promoter CD colorectal cancer gene therapy
通讯作者	Liu, XY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.,xyliu@server.shcnc.ac.cn
英文摘要	Human telomerase reverse transcriptase (hTERT), the catalytic subunit of the telomerase, is transcriptionally upregulated in more than 90% of tumor cells. It may be used as a tool for driving a gene to kill tumors specifically. To test this idea, luciferase reporter gene was used and the results showed that hTERT promoter could restrict the gene expression in the telomerase-positive tumor cells. A tumor-specific expression plasmid phTERT-CD was constructed, in which the E. coli cytosine deaminase (CD) gene was controlled by the hTERT promoter. A colorectal cancer cell line (LoVo) and a normal amnion cell line (WISH) were transfected by this plasmid. It was shown that the expression of the CD gene increased the sensitivity of LoVo cells to the prodrug, 5-fluorocytosine (5FC), over 800-fold, while the sensitivity of WISH cells to 5FC was increased only 6-fold. Mixed cell experiments showed a strong 'bystander effect' on CD-negative cells. Furthermore, a significant anti-tumor effect of the phTERT-CD/5FC system was observed in nude mice bearing mammalian carcinoma induced by s.c. inoculation of LoVo cells when the mice were given 250 mg/kg 5FC twice a day for 10 consecutive days. These results indicated that hTERT promoter could target the suicidal effect of CD gene to tumor cells, and therefore, may be a novel and promising targeting approach to the treatment of cancer.
学科主题	Oncology
类目[WOS]	Oncology
关键词[WOS]	CATALYTIC SUBUNIT HTERT ; HUMAN BONE-MARROW ; TRANSGENE EXPRESSION ; GLIOMA-CELLS ; THERAPY ; CARCINOMA ; ADENOVIRUS ; ACTIVATION ; COMPONENT ; ANTIGEN
收录类别	SCI
语种	英语
WOS记录号	WOS:000177375100029
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2456]
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	Liu, J,Zou, WG,Lang, MF,et al. Cancer-specific killing by the CD suicide gene using the human telomerase reverse transcriptase promoter[J]. INTERNATIONAL JOURNAL OF ONCOLOGY,2002,21(3):661-666.
APA	Liu, J.,Zou, WG.,Lang, MF.,Luo, J.,Sun, LY.,...&Liu, XY.(2002).Cancer-specific killing by the CD suicide gene using the human telomerase reverse transcriptase promoter.INTERNATIONAL JOURNAL OF ONCOLOGY,21(3),661-666.
MLA	Liu, J,et al."Cancer-specific killing by the CD suicide gene using the human telomerase reverse transcriptase promoter".INTERNATIONAL JOURNAL OF ONCOLOGY 21.3(2002):661-666.