Specific activation of sodium iodide symporter gene in hepatoma using alpha-fetoprotein promoter combined with hepatitis B virus enhancer (EIIAPA).
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.


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 1241 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.


CONCLUSIONS
Transduction of the hNIS gene controlled by the novel EIIAPA chimeric promoter successfully induces iodide transport in hepatoma.
Liu
Ren-Shyan
RS
Molecular and Genetic Imaging Core, NRPGM, ROC. rsliu@vghtpe.gov.tw
Hsieh
Ya-Ju
YJ
Ke
Chien-Chih
CC
Chen
Fu-Du
FD
Hwu
Luen
L
Wang
Fu-Hui
FH
Hwang
Jeng-Jong
JJ
Chi
Chin-Wen
CW
Lee
Chen-Hsen
CH
Yeh
Shin-Hwa
SH