Expression and Regulation of the Cell Adhesion Molecule CD44 in Human BreastCancer

摘要

Our laboratory has recently devised two potential gene therapeutic approaches,the utilization of alternative splicing as a control element in the chimeric enzyme/prodrug therapy (CEPT), and dual modulation vectors. Both approaches aim at increasing the tissue-specific expression of gene therapeutic agents. Based on differences in CD44 variant isoform expression between normal and malignant cancer cells, we postulate that selective killing of primary and metastatic cancers may be achieved by utilizing alternative splicing signals of CD44 variant exons as control elements in CEPT. In our colon cancer metastasis to liver model, we developed dual modulation vectors to increase tissue-specific expression of cytosine deaminase (CD) and protect normal cells. The activity of oppositionally inserted albumin promoter is used to downregulate the non-specific expression of CEA promoter in liver cells. We report here our initial efforts to test (1) the activity of chimeric fusion protein CD44/CD in mammalian cells and (2) the activity of dual modulation vector using the CAT report gene.