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Endocrine-Related Cancer 14 (2) 293-303    DOI: 10.1677/ERC-06-0016
Copyright © 2007 by the Society for Endocrinology.
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Induction of multidrug resistance associated protein 2 in tamoxifen-resistant breast cancer cells

 Hoo Kyun Choi, Jin Won Yang, Sang Hee Roh, Chang Yeob Han and Keon Wook Kang

BK21 Project Team, College of Pharmacy, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju 501-759, South Korea

(Requests for offprints should be addressed to K W Kang; Email: kwkang{at}chosun.ac.kr)

H K Choi and J W Yang contributed equally to this work

Acquired resistance to tamoxifen (TAM) is a serious therapeutic problem in breast cancer patients. The transition from chemotherapy-responsive breast cancer cells to chemotherapy-resistant cancer cells is mainly accompanied by the increased expression of multidrug resistance-associated proteins (MRPs). In this study, it was found that TAM-resistant MCF-7 (TAMR-MCF-7) cells expressed higher levels of MRP2 than control MCF-7 cells. Molecular analyses using MRP2 gene promoters supported the involvement of the pregnane X receptor (PXR) in MRP2 overexpression in TAMR-MCF-7 cells. Although CCAAT/enhancer-binding protein ß was overexpressed continuously in TAMR-MCF-7 cells, this might not be responsible for the transcriptional activation of the MRP2 gene. In addition, the basal activities of phosphatidylinositol 3-kinase (PI3-kinase) were higher in the TAMR-MCF-7 cells than in the control cells. The inhibition of PI3-kinase significantly reduced both the PXR activity and MRP2 expression in TAMR-MCF-7 cells. Overall, MRP2 induction plays a role in the additional acquisition of chemotherapy resistance in TAM-resistant breast cancer.






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