Induction of multidrug resistance associated protein 2 in tamoxifen-resistant breast cancer cells.
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 beta 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.
Choi
Hoo Kyun
HK
BK21 Project Team, College of Pharmacy, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju 501-759, South Korea.
Yang
Jin Won
JW
Roh
Sang Hee
SH
Han
Chang Yeob
CY
Kang
Keon Wook
KW
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001141:Aromatase / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000077297:Pregnane X Receptor; D011401:Promoter Regions, Genetic; D011987:Receptors, Steroid / Q000378:metabolism; D013629:Tamoxifen / Q000627:therapeutic use*; D015533:Transcriptional Activation; D015854:Up-Regulation; D000097202:ATP-Binding Cassette Sub-Family B Member 4
D018435:ATP Binding Cassette Transporter, Subfamily B; D018931:Antineoplastic Agents, Hormonal; D001141:Aromatase; D022782:CCAAT-Enhancer-Binding Protein-beta; D019869:Phosphatidylinositol 3-Kinases; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D013629:Tamoxifen; D000097202:ATP-Binding Cassette Sub-Family B Member 4