Back to Search
Start Over
Retrovirus-mediated gene therapy for hepatocellular carcinoma: selective and enhanced suicide gene expression regulated by human alpha-fetoprotein enhancer directly linked to its promoter.
- Source :
-
Cancer gene therapy [Cancer Gene Ther] 1998 Sep-Oct; Vol. 5 (5), pp. 301-6. - Publication Year :
- 1998
-
Abstract
- We have previously reported that a retrovirus vector (LNAF0.3TK) carrying a herpes simplex virus thymidine kinase gene regulated only by the 0.3-kb human alpha-fetoprotein (AFP) promoter provides ganciclovir (GCV)-mediated cytotoxicity in high AFP-producing human hepatoma cells but not in low AFP-producing cells. In the present study, a retrovirus vector (LNAF0.3(E+)TK), in which herpes simplex virus thymidine kinase gene expression is under the control of a human AFP enhancer directly linked to its promoter, was constructed and compared with LNAF0.3(E+)TK. In the intermediate and low AFP-producing human hepatoma cells PLC/PRF/5 and huH1/cl.2, respectively, as well as in the high AFP-producing human hepatoma cells (HepG2), LNAF0.3(E+)TK sensitized these cells to GCV in vitro but did not affect cell growth in nonhepatoma cells (HeLa). In an animal model using athymic mice harboring PLC/PRF/5 cells, GCV treatment resulted in more pronounced growth inhibition in the LNAF0.3(E+)TK virus-infected cells than in the LNAF0.3(E+)TK virus-infected cells. These results indicate that the human AFP enhancer that is directly linked to its promoter involves selective and enhanced tumoricidal activity in gene therapy for hepatocellular carcinoma.
- Subjects :
- Animals
Antineoplastic Agents pharmacology
Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular virology
Cell Division drug effects
Enhancer Elements, Genetic
Ganciclovir pharmacology
Gene Expression Regulation, Neoplastic
Genetic Vectors genetics
Humans
Liver Neoplasms genetics
Liver Neoplasms therapy
Liver Neoplasms virology
Liver Neoplasms, Experimental therapy
Male
Mice
Mice, Inbred BALB C
Promoter Regions, Genetic
Thymidine Kinase genetics
Carcinoma, Hepatocellular therapy
Genetic Therapy methods
Genetic Vectors pharmacology
Retroviridae genetics
alpha-Fetoproteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0929-1903
- Volume :
- 5
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cancer gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 9824049