Gene targeting therapy for oral carcinoma using adrenomedullin antagonisit.

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We have recently reported that intra-tumoral injection of adrenomedullin (AM) antagonist (AMA ; AM(22-52)) peptides significantly reduced the in vivo growth of a pancreatic cancer cell line in SCID mice. In this study, we examined the effects of intra-tumoral and intra-muscular transfers of naked DNA encoding. AMA on the in vivo growth of cancer cell lines. We demonstrated here that the intra-tumoral and intra-muscular transfers of naked DNA encoding AMA induced the regression of a pancreatic cancer cell line and a breast cancer cell line. We further demonstrated that CD31-positive cells completely disappeared from the tumor tissues treated with the intra-tumoral or intra-muscular transfer of naked DNA encoding AMA. These results suggest that the intra-tumoral or intra-muscular transfer of naked DNA encoding AMA might be a promising tool for treating cancersE4orf6 plays an important role in the transcription of cellular and viral mRNAs. We show that E4orf6 interacts with pp32/LAMP and exports pp32/LAMP from the nucleus to the cytoplasm with its binding partner, HuR, which binds to an AU-rich element (ARE) present within many protooncogene and cytokine mRNAs. We found that ARE-mRNAs, such as c-fos,c-myc and Cox-2, were exported to and stabilized in the cytoplasm of E4orf6-expressing cells.The oncodomain of E4orf6 was necessary for both binding to pp32/LAMP and defect for ARE-mRNA. Moreover, inhibition of CRM1-dependent export pathway failed to block the export of ARE-mRNAs mediated by E4orf6. Thus, E4orf6 interacts with pp32/LAMP to modulate the fate of ARE-mRNAs by altering the CRM1-dependent export pathway.