Regulation of MDR1 promoter activity in human breast carcinoma cells by protein kinase C isozymes α and θ

摘要: Increased levels of the protein kinase C (PKC) isoenzymes α and θ occur in conjunction with MDR1 gene expression cells tissues that have acquired a multidrug resistance (MDR) phenotype. Studies using PKC activators or antisense strategies against suggest activation engenders transcription. In this study potential roles PKC-α PKC-θ transcriptional regulation were explored. Human-derived MCF-7 breast cancer lack constitutive at detectable transfected full-length genes driven by ecdysone promoter. Stable transfectants selected use appropriate antibiotics. Treatment these ponasterone A induced was catalytically active underwent translocation down-regulation on exposure to 12-O-tetradecanoyl-13-phorbol acetate (TPA). These used analyse PKC-mediated promoter further transient transfection either 1073 bp deletion fragments thereof −8 bp, each linked chloramphenicol acetyl transferase (CAT) reporter gene. expressing TPA caused all −29 bp. This finding suggests TPA-inducible transcription mediated through responsive factor early growth response 1 (EGR-1) region may be due PKC-α. contrast, activated only two fragments, −982 −612 bp. The effect attenuated inhibitor GF 109203X. data can regulated PKC-θ. results support search for therapeutic directed specifically ameliorate tumours cytotoxic agents.