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.

Abstract

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.

• Authors: Beibei Wang, Gang Chen, Jianfeng Zhou, Peng Wu, Danfeng Luo, Xiaoyuan Huang, Tao Zhu, Zhiqiang Han, Gang Xu, Shixuan Wang, Yunping Lu, Ding Ma
• Journal: Cancer letters (Cancer Lett) Vol. 248 Issue 2 Pg. 299-307 (Apr 18 2007) ISSN: 0304-3835 [Print] Ireland
• PMID: 17166654 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CLMP protein, human
• Coxsackie and Adenovirus Receptor-Like Membrane Protein
• Receptors, Virus

Topics

• Adenoviridae Infections (therapy)
• Blotting, Western
• Cell Line, Tumor
• Coxsackie and Adenovirus Receptor-Like Membrane Protein
• Female
• Flow Cytometry
• Gene Expression
• Genetic Therapy (methods)
• Humans
• In Vitro Techniques
• Ovarian Neoplasms (virology)
• Receptors, Virus (chemistry, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Transfection
• Up-Regulation