RT Journal Article
SR Electronic
T1 Specific Activation of Sodium Iodide Symporter Gene in Hepatoma Using Alpha-fetoprotein Promoter Combined with Hepatitis B Virus Enhancer (EIIAPA)
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 211
OP 221
VO 29
IS 1
A1 REN-SHYAN LIU
A1 YA-JU HSIEH
A1 CHIEN-CHIH KE
A1 FU-DU CHEN
A1 LUEN HWU
A1 FU-HUI WANG
A1 JENG-JONG HWANG
A1 CHIN-WEN CHI
A1 CHEN-HSEN LEE
A1 SHIN-HWA YEH
YR 2009
UL http://ar.iiarjournals.org/content/29/1/211.abstract
AB Background: This study aimed to develop a novel tumor-specific promoter gene linking sodium iodide symporter (NIS) gene to specifically target hepatocellular carcinoma in a mouse tumor model. Materials and Methods: A tumor-specific chimeric promoter for alpha-fetoprotein gene (AFP) was combined with hepatitis B virus (HBV) enhancer II to investigate radioiodine uptake in vitro and in vivo in hepatoma (HepG2) and nonhepatoma (ARO) cell lines after transfer of hNIS gene. A lentiviral vector carrying the hNIS gene was employed in vitro and in vivo. Radionuclide imaging was acquired for 30 min at 60 min after administration of 124I to monitor hNIS gene expression in vivo using microPET. Results: The highest radioiodide uptake of ARO and HepG2 clones which stably expressed hNIS gene were 87- and 208-fold higher than that of parental cells, respectively. After infection of lentivirus, hNIS gene controlled by cytomegavirus (CMV) promoter was expressed in both ARO and HepG2 cells, and hNIS gene induction by EIIAPA promoter was higher than by CMV promoter in HepG2 cells but not in ARO cells. A similar result was observed in vivo, hNIS controlled by CMV promoter was highly expressed in both HepG2 and ARO tumors. The HepG2 tumor multi-infected with LV-EIIAPA-hNIS virus specifically, but the ARO tumor did not activate the EIIAPA promoter and further express the hNIS protein. Conclusion: Transduction of the hNIS gene controlled by the novel EIIAPA chimeric promoter successfully induces iodide transport in hepatoma. Copyright© 2009 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved