mechanism of drug resistance in breast cancer : the correlation between steroid and xenobiotic receptor (SXR) and UDP-glucuronosyltransferase (UGT)

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Steroid and xenobiotic receptor (SXR) is ligand-activated transcription factor, which is a member of the nuclear hormone receptor superfamily. We have reported that SXR activated the expression of CYP3A4 and MDR-I, playing a part of phase I stage in drug metabolism, in breast cancer cells lines. Conjugation is the phase II stage of drug metabolism, and is catalyzed by UDP-glucuronosyltransferase (UGT). So, we investigated the correlation between SXR and UGT in breast cancer cells.We confirmed the expression of UGT1A1, UGT1A4 and UGT2B7 mRNA by RT-PCR inbreast cancer cell lines. UGT1A1 can conjugate estrogens. UGT1A4 and UGT2B7 canconjugate tamoxifen, which is the drug for hormone therapy of for breast cancer. It wasreported thatSince the expression of UGT1A1 and UGT1A4 are is regulated by SXR inhepatocellular carcinoma cell lines. W, we also studied and confirmed the up-regulation ofUGT1A4 expression by SXR in breast cancer cell lines. Furthermore, Wwe investigated theexpression levels of UGT1A1, UGT1A4 and UGT2B7 in breast cancer tissues by real-timeRT-PCR, using the specimens from 70 breast cancer patients, who were undergone theoperation in Gunma University Hospital between in 2007 and 2008. There was were nocorrelations between SXR and UGT1A1, and. There was also no correlation between SXRand UGT1A4 mRNA levels. But wWe could not measure the expression level of UGT2B7mRNA. In summary, Wwe could not obtain fund the evidence for regulation of UGT by SXRfrom this experiment plan. Because there is a fewseveral evidences of that such regulation,so we need more experiment.more study may be necessary.