P-glycoprotein down-regulates expression of breast cancer resistance protein in a drug-free state

This study investigated whether P-glycoprotein ( Pgp) and breast cancer resistance protein ( BCRP) are linked in terms of expression. RT- PCR and Western blot analyses showed that the lung cancer cell line SK- MES- 1/ WT expressed BCRP. In a drug- free state, BCRP expression was signi. cantly down- regulated in doxorubicin- resistant SK- MES- 1/ DX1000 cells overexpressing Pgp. Pharmacological inhibitors ( PSC833 or verapamil) or siRNA for Pgp inhibited the down- regulation of BCRP, which was con. rmed by confocal microscopy. PSC833 induced the phosphorylation of c- Jun NH2- terminal kinase ( JNK) and c- Jun, while the JNK inhibitor SP600125 inhibited this e. ect. Dominant negative c- Jun decreased the expression of BCRP, but increased that of Pgp. These results indicate that Pgp down- regulates BCRP expression in a drug- free state in which JNK/ c- Jun is involved. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.