The novel mechanism of the potentiation of estrogen action by steroid and xenobiotic receptor (SXR) in breast cancer cells.

类固醇和异生素受体（SXR）在乳腺癌细胞中增强雌激素作用的新机制。

• 批准号: 17591319
• 负责人: HORIGUCHI Jun
• 金额: $ 2.24万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591319/
• 关键词: Breast cancer; SXR; ER; corepressor; SMRT

Estrogen receptor (ER) is a key regulator of proliferation and differentiation in breast cancer cells. Previous studies have shown that its action may be modulated by other nuclear factors. One such candidate may be steroid and xenobiotic receptor (SXR) that is expressed in neoplastic breast tissue. In the present study, the effect of SXR on 17-estradiol (E_2)-induced transcription through ER was studied. SXR augmented ER-mediated transcription in the presence of E_2 in MCF-7 breast cancer-derived cells and CV-1 fibroblast-derived cells. On the other hand, SXR alone did not affect the estrogen response element (ERE)-containing promoter activity in CV-1 cells. SXR did not directly bind to ER nor ERE in vivo and in vitro, indicating that SXR may affect ER-mediated transcription by altering cofactor binding to ER. Although SCR did not alter the binding between ER and p300/CBP interacting protein (p/CIP), it decreased the binding of a specific corepressor, silencing mediator of retinoid and thyroid hormone receptors (SMRT) to liganded ER by mammalian two-hybrid, GST pull down and a newly developed liquid fluorescence DNA pull down assays. These results indicate that SXR augmented ER-mediated transcription by squelching SMRT. Thus, the expression of SXR in breast cancer cells may alter the ER signaling, which may play crucial role for growth and differentiation of breast cancer cells.

雌激素受体（ER）是乳腺癌细胞增殖和分化的关键调控因子。先前的研究表明，它的作用可能受到其他核因子的调节。一个这样的候选者可能是在肿瘤乳腺组织中表达的类固醇和异种受体（SXR）。本研究研究了SXR对17-雌二醇（E_2）诱导的ER转录的影响。在MCF-7乳腺癌来源细胞和CV-1成纤维细胞来源细胞中，在E_2存在的情况下，SXR增强了er介导的转录。另一方面，单独使用SXR不影响CV-1细胞中含有雌激素反应元件（ERE）的启动子活性。在体内和体外，SXR不直接与ER和ERE结合，表明SXR可能通过改变ER的辅因子结合来影响ER介导的转录。虽然SCR没有改变ER与p300/CBP相互作用蛋白（p/CIP）之间的结合，但通过哺乳动物双杂交、GST拉下和新开发的液体荧光DNA拉下试验，SCR降低了特异性协同抑制因子、类视黄醇和甲状腺激素受体沉默介质（SMRT）与配体ER的结合。这些结果表明，SXR通过抑制SMRT增强了er介导的转录。因此，乳腺癌细胞中SXR的表达可能会改变内质网信号，这可能对乳腺癌细胞的生长和分化起到至关重要的作用。

项目成果

Low dose hydroxylated PCB induces c-Jun expression in PC12 cells.

• DOI: 10.1016/j.neuro.2005.09.005
• 发表时间: 2006-03
• 期刊: Neurotoxicology
• 影响因子: 3.4
• 作者: N. Shimokawa;W. Miyazaki;T. Iwasaki;N. Koibuchi

Retinoid-related receptor(ROR)α mRNA expression is altered in the brain of male mice lacking all ligand-binding thyroid hormone receptor (TR) isoforms.

缺乏所有配体结合甲状腺激素受体 (TR) 亚型的雄性小鼠大脑中，类维生素A相关受体 (ROR)α mRNA 表达发生改变。

• 发表时间: 2005
• 期刊: Endorine 26
• 作者: Vasudevan N;Kia HK;Hadjimarkou M;Koibuchi N;Chin WW;Forrest D;Vennstrom B;Pfaff DW
• 通讯作者: Pfaff DW

Significance of local recurrence as a prognostic factor in the treatment of breast cancer

局部复发作为乳腺癌治疗预后因素的意义

• 发表时间: 2006
• 期刊: Anticancer Res 26
• 作者: Horiguchi J;Koibuchi Y;Yoshida T;Takata D;Kikuchi M;Rokutanda N;Nagaoka R;Iino Y;Sakurai H;Morishita Y.
• 通讯作者: Morishita Y.

乳房温存手術, 乳房温存療法の成績.よくわかる乳癌のすべて(飯野佑一、園尾博司、編集)

您需要了解的有关乳腺癌的保乳手术和保乳治疗的结果（Yuichi Iino、Hiroshi Sonoo，编辑）

• 发表时间: 2006
• 作者: 飯野佑一;鯉淵幸生;鯉淵典之;鯉淵 典之;飯野 佑一;飯野 佑一;堀口 淳
• 通讯作者: 堀口 淳

The adrenal gland is a source of stress-induced circulating IL-18

• DOI: 10.1016/j.jneuroim.2005.11.001
• 发表时间: 2006-03-01
• 期刊: JOURNAL OF NEUROIMMUNOLOGY
• 影响因子: 3.3
• 作者: Sugama, S;Wang, N;Conti, B
• 通讯作者: Conti, B