title: The EIIAPA chimeric promoter for tumor specific gene therapy of hepatoma.
abstract: OBJECTIVE
  For targeted imaging and therapy of hepatocellular carcinoma (HCC), we established a chimeric promoter (EIIAPA) containing alpha-fetoprotein (AFP) promoter and hepatitis B virus enhancer II (EIIA) to control downstream expression of reporter and therapeutic genes.
  
  
  METHODS
  We combined AFP promoter and EIIA to establish a chimeric EIIAPA promoter, then developed a bi-cistronic plasmid vector containing HSV1-tk and luciferase genes controlled by EIIAPA to stably transfect HCC cells. The selective transcriptional activity of EIIAPA was assayed by bioluminescence imaging (BLI) and the function of EIIAPA was determined by in vivo microPET and BLI.
  
  
  RESULTS
  The luciferase expression driven by EIIAPA was higher than that driven by AFP promoter in HCC cell lines. EIIAPA-tk induced cytotoxicity was observed only in HepG2 cells. Accumulation of ¹³¹I-FIAU and bioluminescent signal were detected on HepG2 tumors but not in parental tumors. The HepG2 tumors derived from lentiviral-transduced EIIAPA-tk expressing cells accumulated ¹²⁴I-FIAU whereas the ARO tumors did not. The transfected HepG2 tumors expressed adequate EIIAPA-controlled HSV1-TK and the tumor regressed after ganciclovir treatment.
  
  
  CONCLUSIONS
  The chimeric EIIAPA is a potential candidate promoter for targeted imaging and gene therapy of HCC.
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ya-Ju
authors.initials: YJ
authors.lastname: Hsieh
authors.forename: Fu-Du
authors.initials: FD
authors.lastname: Chen
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Ke
authors.forename: Hsin-Ell
authors.initials: HE
authors.lastname: Wang
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Huang
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Hou
authors.forename: Kang-Ping
authors.initials: KP
authors.lastname: Lin
authors.forename: Juri G
authors.initials: JG
authors.lastname: Gelovani
authors.forename: Ren-Shyan
authors.initials: RS
authors.lastname: Liu
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005455:Fluorescent Antibody Technique; D015774:Ganciclovir / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D015316:Genetic Therapy; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000378:metabolism; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D057054:Molecular Imaging; D041681:NIH 3T3 Cells; D055096:Optical Devices; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011877:Radionuclide Imaging; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D000509:alpha-Fetoproteins / Q000235:genetics* / Q000627:therapeutic use*
chemical_list: D000509:alpha-Fetoproteins; D008156:Luciferases; D015774:Ganciclovir