Retrovirus-Mediated Gene Therapy for Hepatocellular Carcinoma with Reversely Oriented Therapeutic Gene Expression Regulated by α-Fetoprotein Enhancer/Promoter
| Autor: | Katsumi Eguchi, Yuji Kato, Akio Ido, Nobuko Ishii, Hiroki Ishikawa, Kazuhiko Nakao, Toshihito Ueki, Shotaro Tsuruta, Keisuke Nakata, F Mawatari |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Therapeutic gene modulation Carcinoma Hepatocellular Recombinant Fusion Proteins Genetic enhancement Genetic Vectors Biophysics Mice Nude Regulatory Sequences Nucleic Acid Biology Thymidine Kinase Biochemistry Viral vector Mice chemistry.chemical_compound Gene expression Tumor Cells Cultured Animals Humans Simplexvirus Northern blot Promoter Regions Genetic Enhancer Molecular Biology Mice Inbred BALB C Liver Neoplasms Genetic Therapy Cell Biology Molecular biology digestive system diseases Enhancer Elements Genetic Retroviridae Gene Expression Regulation chemistry Thymidine kinase Cancer research alpha-Fetoproteins Growth inhibition Retroviridae Infections |
| Zdroj: | Biochemical and Biophysical Research Communications. 287:1034-1040 |
| ISSN: | 0006-291X |
| DOI: | 10.1006/bbrc.2001.5684 |
| Popis: | In the present study, to achieve more selective and efficient therapeutic gene expression in hepatoma cells, we compared the therapeutic efficacies of the retroviral vectors expressing the herpes simplex virus thymidine kinase (HSV-tk) gene by the α-fetoprotein (AFP) enhancer/promoter in the forward (LNAFE0.3TK) and reverse (LN[AFE0.3TK]R) orientation to the vector long terminal repeats. By Northern blotting, the level of the HSV-tk mRNA in LN[AFE0.3TK]R-infected HepG2 human hepatoma cells was much higher than that in LNAFE0.3TK-infected cells. Consistent with this, LN[AFE0.3TK]R infection into HepG2 cells caused a greater cytotoxicity by ganciclovir exposure together with a stronger bystander effect than LNAFE0.3TK infection. In an animal model, intratumorous injection of LN[AFE0.3TK]R with ganciclovir treatment resulted in pronounced growth inhibition of HepG2 tumor. Thus, the reversely oriented therapeutic gene expression under the control of AFP enhancer/promoter is a possible candidate for the retrovirus-mediated gene therapy for hepatocellular carcinoma. |
| Databáze: | OpenAIRE |
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