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

乳腺癌耐药机制：类固醇和异生素受体（SXR）与UDP-葡萄糖醛酸基转移酶（UGT）之间的相关性

• 批准号: 19790912
• 负责人: ODAWARA Hiroki
• 金额: $ 2.48万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19790912/
• 关键词: 乳癌; 薬物代謝; UGT; SXR; エストロゲン; 核内ホルモン受容体; グルクロンサン抱合

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.

类固醇和异生素受体（Steroid and xenobiotic receptor，SXR）是一种配体激活的转录因子，属于核激素受体超家族成员。我们报道了SXR可激活乳腺癌细胞系CYP 3A 4和MDR-I的表达，参与药物代谢的I相阶段。结合是药物代谢的第二阶段，由UDP-葡萄糖醛酸转移酶（UGT）催化。因此，本研究通过RT-PCR检测乳腺癌细胞系中UGT 1A 1、UGT 1A 4和UGT 2B 7 mRNA的表达，探讨SXR和UGT在乳腺癌细胞中的相关性。UGT 1A 1可以结合雌激素。UGT 1A 4和UGT 2B 7可与乳腺癌激素治疗药物他莫昔芬结合。据报道，UGT 1A 1和UGT 1A 4的表达受SXR肝癌细胞系的调控。我们还研究并证实了SXR对乳腺癌细胞系UGT 1A 4表达的上调作用。此外，我们使用2007年至2008年在群马大学医院接受手术的70例乳腺癌患者的标本，通过实时RT-PCR检测了UGT 1A 1、UGT 1A 4和UGT 2B 7在乳腺癌组织中的表达水平。SXR与UGT 1A 1、UGT 1A 1、UGT 1A 1之间无相关性。SXR与UGT 1A 4 mRNA表达之间也无相关性。但未检测到UGT 2B 7 mRNA的表达。综上所述，本实验方案未能获得SXR调控UGT的充分证据。由于这种调节的证据很少，所以我们还需要更多的实验，更多的研究可能是必要的。

项目成果

乳癌細胞におけるPCBによる核内ホルモン受容体を介する転写の活性化-

乳腺癌细胞中多氯联苯通过核激素受体激活转录

• 发表时间: 2007
• 作者: Sajdel-Sulkowska E;Xu M;Koibuchi N;Koibuchi N;鯉淵典之;鯉淵典之;Koibuchi N;Koibuchi N;岩崎俊晴;鯉淵幸生;鯉淵典之;岩崎俊晴;堀口 淳;鯉淵幸生;小田原宏樹;堀口 淳;鯉淵幸生;Koibuchi N;Koibuchi N;Koibuchi N;Iwasaki T;小田原宏樹;堀口 淳;堀口 淳;岩崎俊晴;堀口 淳;小田原宏樹;堀口 淳;堀口淳;堀口淳;堀口淳;堀口淳;堀口淳;鯉淵幸生;鯉淵幸生;鯉淵幸生;小田原宏樹;小田原宏樹;Iwasaki T;岩崎俊晴;岩崎俊晴;岩崎俊晴;岩崎俊晴;Koibuchi N;Koibuchi N;Koibuchi N;Koibuchi N;鯉淵典之;岩崎俊晴;Koibuchi N;鯉淵幸生;鯉淵幸生;堀口 淳;鯉淵幸生;Koibuchi N;Koibuchi N;堀口 淳;鯉淵幸生;小田原宏樹
• 通讯作者: 小田原宏樹

乳癌組織における核内ホルモン受容体RORα発現の意義

乳腺癌组织中核激素受体RORα表达的意义

• 发表时间: 2009
• 作者: 小田原宏樹;堀口淳;岩崎俊晴;鯉淵幸生;六反田奈和;長岡りん;時庭英彰;樋口徹;飯野祐一;鯉淵典之;竹吉泉;小田原宏樹
• 通讯作者: 小田原宏樹

Activation of Aromatase Expression by Retinoic Acid Receptor-related Orphan Receptor (ROR)αin Breast Cancer Cells: identification of a novel ROR response elementIDENTIFICATION OF A NOVEL ROR RESPONSE ELEMENT.

乳腺癌细胞中视黄酸受体相关孤儿受体 (ROR)α 激活芳香酶表达：新型 ROR 反应元件的鉴定新型 ROR 反应元件的鉴定。

• 发表时间: 2009
• 期刊: J Biologic Chem 284
• 作者: Hiroki Odawara;Toshiharu Iwasaki;Jun Horiguchi;Nana Rokutanda;Kazumi Hirooka;Wataru Miyazaki;Yukio Koibuchi;Noriaki Shimokawa;Yuichi Iino;Izumi Takeyoshi;Noriyuki Koibuchi
• 通讯作者: Noriyuki Koibuchi

核内受容体RORαによる乳癌細胞増殖能の活性化

核受体RORα激活乳腺癌细胞增殖能力

• 发表时间: 2009
• 作者: 小田原宏樹;堀口淳;岩崎俊晴;鯉淵幸生;六反田奈和;長岡りん;時庭英彰;樋口徹;飯野祐一;鯉淵典之;竹吉泉
• 通讯作者: 竹吉泉

核内ホルモン受容体RORαによるアロマターゼ遺伝子の新たな活性化機序

核激素受体RORα激活芳香酶基因的新机制

• 发表时间: 2009
• 作者: 小田原宏樹;堀口淳;岩崎俊晴;鯉淵幸生;六反田奈和;長岡りん;時庭英彰;樋口徹;飯野祐一;鯉淵典之;竹吉泉;小田原宏樹;小田原宏樹;小田原宏樹;小田原宏樹
• 通讯作者: 小田原宏樹