Deletion of the intracellular domain of coxsackie and adenovirus receptor (CAR) enhances the expression of itself and boosts the efficiency of current adenovirus-mediated gene therapy in ovarian cancer cell lines in vitro.
The failure of adenovirus-mediated gene therapy often derives from the absence of coxsackie and adenovirus receptor (CAR) expression in target cells. We hypothesize that the slight up-regulation of CAR expression might boost the effect of adenovirus-mediated gene therapy in ovarian cancer. To test this hypothesis, we transfected full-length and intracellular-domain-deleted (tailless) CAR plasmids into CAR-deficient ovarian cancer cell line SKOV3. We observed significant elevations of the in vitro killing effect of Adv-TK and oncolytic adenovirus-mediated cytopathic effect (CPE) in transfected sub-clones, and tailless-transfected SKOV3 showed higher CAR expressions than full-length CAR-transfected cells. We conclude that the extracellular domain of CAR is essential for adenovirus-based gene therapy and, furthermore, that its intracellular domain might play an important role in the regulation of its own expression.
Wang
Beibei
B
Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Chen
Gang
G
Zhou
Jianfeng
J
Wu
Peng
P
Luo
Danfeng
D
Huang
Xiaoyuan
X
Zhu
Tao
T
Han
Zhiqiang
Z
Xu
Gang
G
Wang
Shixuan
S
Lu
Yunping
Y
Ma
Ding
D
D000257:Adenoviridae Infections / Q000628:therapy*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D010051:Ovarian Neoplasms / Q000821:virology*; D011991:Receptors, Virus / Q000737:chemistry* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation
C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus