Transfection with protein kinase C alpha confers increased multidrug resistance to MCF-7 cells expressing P-glycoprotein.

摘要: Cross-resistance to anticancer drugs, termed multidrug resistance (mdr), has been functionally associated with the expression of a plasma membrane energy-dependent efflux pump, P-glycoprotein, product mdr1 gene. When MCF-7 breast carcinoma cells were transfected human gene (BC-19 cells), they expressed levels P-glycoprotein equivalent those selected for doxorubicin (MCF-7/ADR) but exhibited 10- 50-fold less and vinblastine. We have now demonstrated that when BC-19 stably protein kinase C alpha (PKC alpha), vinblastine was increased; wild-type PKC did not exhibit any change in drug resistance. Increased alpha-transfected enhanced activity phosphorylation decreased accumulation. The activator, phorbol dibutyrate, further increased stimulated phosphorylation. These results demonstrate transfection P-glycoprotein-expressing resulted mdr may served as an important modulator this process.