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
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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. |
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