title: Gene therapy for hepatocellular carcinoma based on tumour-selective suicide gene expression using the alpha-fetoprotein (AFP) enhancer and a housekeeping gene promoter.
abstract: The aim of this study was to examine whether the human alpha-fetoprotein (AFP) enhancer could be used to induce hepatocellular carcinoma (HCC)-selective expression of the herpes simplex virus thymidine kinase (HSV-tk) gene which is under the control of the phosphoglycerate kinase (pgk) promotor. The human AFP enhancer was linked with the non-tissue-specific, human housekeeping pgk promoter in a retroviral vector. AFP-producing HCC cells infected with retroviruses carrying the HSV-tk gene under the control of the AFP enhancer/pgk promoter were much more susceptible to the prodrug, ganciclovir (GCV), than those infected with the same retroviruses without the AFP enhancer. Non-HCC cells infected with retroviruses carrying the HSV-tk gene under the control of the AFP enhancer/pgk promoter exhibited profoundly increased resistance to GCV compared with those infected with the same retroviruses without the AFP enhancer. Northern blot analysis revealed that the AFP enhancer caused enhanced HSV-tk expression in AFP-producing HCC cells and suppressed HSV-tk expression in non-HCC cells. Our results indicate that the AFP enhancer could give HCC selectivity to the pgk promoter, and that this novel strategy may be useful for HCC-selective cancer gene therapy.
authors.affiliation: Department of Microbiology, Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, China.
authors.forename: G
authors.initials: G
authors.lastname: Cao
authors.forename: S
authors.initials: S
authors.lastname: Kuriyama
authors.forename: J
authors.initials: J
authors.lastname: Gao
authors.forename: T
authors.initials: T
authors.lastname: Nakatani
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: Yoshiji
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.forename: H
authors.initials: H
authors.lastname: Kojima
authors.forename: Y
authors.initials: Y
authors.lastname: Dong
authors.forename: H
authors.initials: H
authors.lastname: Fukui
authors.forename: J
authors.initials: J
authors.lastname: Hou
mesh_terms: D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D004742:Enhancer Elements, Genetic; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008113:Liver Neoplasms / Q000628:therapy*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000235:genetics*
chemical_list: D000509:alpha-Fetoproteins