title: Cre/loxP system controlled by specific promoter for radiation-mediated gene therapy of hepatoma.
abstract: BACKGROUND
  To specifically target malignant cells, cancer gene therapy needs to combine highly selective gene delivery with highly specific gene expression. In this study, hepatitis B virus (HBV) enhancer II was combined with alpha-fetoprotein (AFP) promoter which selectively controls the Cre/loxP system in hepatoma.
  
  
  METHODS
  pE4luc, pE4Tk, EIIAPA-Cre and E4CMV-STOP-Tk constructs and AFP promoter combined with HBV enhancer were constructed and transfected into HepG2, HeLa and NIH-3T3 cell lines.
  
  
  RESULTS
  The E4 enhancer showed the highest luciferase gene expression at a dose range of 5 approximately 7 Gy after 60 hours irradiation. The EIIAPA chimeric promoter which controls the Cre/loxP system provided high specificity only to the hepatoma cells. In addition, the E4 response to radiation encoded more Herpes simplex virus thymidine kinase (HSV1-Tk) protein and killed more tumor cells.
  
  
  CONCLUSIONS
  The chimeric EIIAPA promoter can precisely control the Cre/loxP switch and the radiation effect on the EIIAPA-Cre and E4CMV-STOP-Tk system shows promising results in terms of cell survival of hepatocellular carcinoma (HCC).
authors.affiliation: School of Medical Technology and Engineering, Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei City, Taiwan, ROC.
authors.forename: Ya-Ju
authors.initials: YJ
authors.lastname: Hsieh
authors.forename: Ren-Shyan
authors.initials: RS
authors.lastname: Liu
authors.forename: Luen
authors.initials: L
authors.lastname: Hwu
authors.forename: Chien Chih
authors.initials: CC
authors.lastname: Ke
authors.forename: Fu Hui
authors.initials: FH
authors.lastname: Wang
authors.forename: Hsin-Ell
authors.initials: HE
authors.lastname: Wang
authors.forename: Fu-Du
authors.initials: FD
authors.lastname: Chen
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D002470:Cell Survival; D004742:Enhancer Elements, Genetic / Q000528:radiation effects*; D015774:Ganciclovir / Q000494:pharmacology; D015316:Genetic Therapy / Q000379:methods*; D006367:HeLa Cells; D006515:Hepatitis B virus / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000235:genetics; D006801:Humans; D019426:Integrases / Q000235:genetics*; D008113:Liver Neoplasms / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic; D011827:Radiation; D013937:Thymidine Kinase / Q000235:genetics; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D000509:alpha-Fetoproteins / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D000509:alpha-Fetoproteins; D013937:Thymidine Kinase; C045073:Cre recombinase; D019426:Integrases; D015774:Ganciclovir