Regulation of C-myc Gene Expression by Potassium Channel Blocker Quindine in MCF-7 Human Breast Cancer Cell Line

摘要

C-myc is a protooncogene, that plays an important role in regulation of cell cycle progression, cellular differentiation and apoptosis. Its abnormal expression was reported in 32% of breast cancers and tumorigenic properties of c-myc overexpression was confirmed by both in vitro and in vivo models of breast cancer. Hence, it is important to understand the precise molecular mechanisms of c-myc regulation. The goal of this proposal is to elucidate how depolarization of the membrane potential in response to potassium channel blocking agent quinidine regulates expression of c-myc gene. Specific aim Number 1 was to test effects of quinidine on c-myc promoter activity in transient reporter gene assay. We mapped 614 bp minimal region of c-myc promoter, that is sufficient to confer responsiveness to quinidine. Fine mapping of this region using PCR and characterization of the nature of DNA/protein(s) interaction in that region are our next goals. Specific aim Number 2 was to test effects of quinidine on c-myc transcription rate using nuclear run-on assay. This aim remained unchanged and will be completed within the proposed time schedule. The significance of this proposal is that its results will improve our understanding of c-myc gene regulation and might discover new targets for breast cancer therapy.