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The efficacy of adenovirus vector-based cancer gene therapy is controversial. Low transduction is believed to be one of the main barriers as expression of coxsackie and adenovirus receptor (CAR) on tumor cells were frequently reduced, and the increasing tumor cell expression of car thus offering promising opportunity for more effective adenovirus-based treatment. Here, we showed that CAR expression varied in colon carcinomas, both in primary tumors and lymphonode metastasis, with decreased expression in 75.8% of primary tumors. When tumor is more than 5 cm in diameter the CAR expression decreased more frequently. Proteasome inhibitor MG-132 could induce CAR expression in colon carcinoma cells, accompanied with enhanced adenovirus vector transfer, target gene expression, and oncolysis. Our data provide a rational basis for evluating CAR expression in tumors and pretreatment with CAR conditioner prior to adenovirus vector-based gene therapy.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA