Gene therapy for oral squamous cell carcinoma targeting tumor specific promoter activation

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Oral squamous cell carcinoma is the mostcommon malignant tumor in oral and maxillofacial region, and has a property that oral carcinoma is able to be recognized macroscopy because of the superficial occurrence of tumors. This characteristics contribute to the gene targeting therapy.First, we examined E1AF expression in normal and tumor tissues. E1AF is anete-oncogene family transcription factor, and we have noted that E1AF can upregulate promoter activities of several matrix metalloproteinase (MMP) genes and showed that invasive potentials of oral squamous cell carcinoma-derived cell lines are correlated with expression of E1AF and MMPs. We analyzed the E1AF expression in cell lines and resected tumors of non-small-cell lung cancers (NSCLC). Fifteen out of 17 cell lines of NSCLC and 12 of 19 tumors expressed E1AF mRNA while normal lung tissue and concomitant normal cells within tumors did not express E1AF mRNA. Similar results were obtained in oral carcinoma and normal tissues. RT-PCR was utilizedto examine the expression of E1AF. Among the 27 patients, E1AF was detected in 15 cases and was not detected in normal tissues.Bnip3 is a pro-apoptotic molecule that contains BH3 and trans-membrane ? domains. BH3 only proteins are now thought to be the initiator of apoptotic signals. Our results suggest that BnipS induces apoptosis by recruiting caspases onto mitochondrial membrane through TM domain.Bik, a BH3 only molecule, expressing adenovirus vector driven by E1AF promoter was reconstructed (Ad-F-Bik). SiHa, a squamous cell carcinoma cell line was transplanted into nude mice. Ad-F-Bik was applied in vivo tumors twice a week. Tumor growth was inhibited by application of Ad-F-Bik, and apoptosis of tumor cells was induced.These results indicate that gene therapy targeting tumor specific expressing molecule is effective using adenovirus vector.