Estrogen receptor alpha 46 is reduced in tamoxifen resistant breast cancer cells and re-expression inhibits cell proliferation and estrogen receptor alpha 66-regulated target gene transcription.

Klinge CM; Riggs KA; Wickramasinghe NS; Emberts CG; McConda DB; Barry PN; Magnusen JE

首页> 外文期刊>Molecular and Cellular Endocrinology >Estrogen receptor alpha 46 is reduced in tamoxifen resistant breast cancer cells and re-expression inhibits cell proliferation and estrogen receptor alpha 66-regulated target gene transcription.

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Estrogen receptor alpha 46 is reduced in tamoxifen resistant breast cancer cells and re-expression inhibits cell proliferation and estrogen receptor alpha 66-regulated target gene transcription.

机译：在他莫昔芬耐药的乳腺癌细胞中雌激素受体α46降低，并且再表达抑制细胞增殖和雌激素受体α66调节的靶基因转录。

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Resistance to endocrine therapy is a major clinical problem in breast cancer. The role of ERalpha splice variants in endocrine resistance is largely unknown. We observed reduced protein expression of an N-terminally truncated ERalpha46 in endocrine-resistant LCC2, LCC9, and LY2 compared to MCF-7 breast cancer cells. Transfection of LCC9 and LY2 cells with hERalpha46 partially restored growth inhibition by TAM. Overexpression of hERalpha46 in MCF-7 cells reduced estradiol (E(2))-stimulated endogenous pS2, cyclin D1, nuclear respiratory factor-1 (NRF-1), and progesterone receptor transcription. Expression of oncomiR miR-21 was lower in TAM-resistant LCC9 and LY2 cells compared to MCF-7 cells. Transfection with ERalpha46 altered the pharmacology of E(2) regulation of miR-21 expression from inhibition to stimulation, consistent with the hypothesis that hERalpha46 inhibits ERalpha activity. Established miR-21 targets PTEN and PDCD4 were reduced in ERalpha46-transfected, E(2)-treated MCF-7 cells. In conclusion, ERalpha46 appears to enhance endocrine responses by inhibiting selected ERalpha66 responses.

机译：对内分泌治疗的抗性是乳腺癌的主要临床问题。 ERalpha剪接变体在内分泌抗性中的作用很大程度上未知。我们观察到与MCF-7乳腺癌细胞相比，内分泌抗性LCC2，LCC9和LY2中N末端截短的ERalpha46的蛋白表达降低。用hERalpha46转染LCC9和LY2细胞可部分恢复TAM对生长的抑制作用。 hERalpha46在MCF-7细胞中的过表达减少了雌二醇（E（2））刺激的内源性pS2，细胞周期蛋白D1，核呼吸因子1（NRF-1）和孕激素受体的转录。与MCF-7细胞相比，在TAM耐药LCC9和LY2细胞中，oncomiR miR-21的表达较低。用ERalpha46转染从抑制到刺激改变了miR-21表达的E（2）调节的药理学，与hERalpha46抑制ERalpha活性的假设一致。已建立的miR-21目标PTEN和PDCD4在ERalpha46转染的E（2）处理的MCF-7细胞中减少。总之，ERalpha46似乎通过抑制选定的ERalpha66反应来增强内分泌反应。

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《Molecular and Cellular Endocrinology》 |2010年第2期|共9页
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Klinge CM; Riggs KA; Wickramasinghe NS; Emberts CG; McConda DB; Barry PN; Magnusen JE;
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中图分类内分泌腺疾病及代谢病;
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1. Estrogen receptor alpha 46 is reduced in tamoxifen resistant breast cancer cells and re-expression inhibits cell proliferation and estrogen receptor alpha 66-regulated target gene transcription. [J] . Klinge CM, Riggs KA, Wickramasinghe NS, Molecular and Cellular Endocrinology . 2010,第2期

机译：在他莫昔芬耐药的乳腺癌细胞中雌激素受体α46降低，并且再表达抑制细胞增殖和雌激素受体α66调节的靶基因转录。
2. MicroRNA-497 downregulation contributes to cell proliferation, migration, and invasion of estrogen receptor alpha negative breast cancer by targeting estrogen-related receptor alpha [J] . Han Li, Liu Bo, Jiang Lixi, Tumour biology : . 2016,第10期

机译：MicroRNA-497下调通过靶向雌激素相关受体α促进细胞增殖，迁移和侵袭雌激素受体α阴性乳腺癌
3. Apigenin inhibits antiestrogen-resistant breast cancer cell growth through estrogen receptor-alpha-dependent and estrogen receptor-alpha-independent mechanisms. [J] . Long X, Fan M, Bigsby RM, Molecular cancer therapeutics . 2008,第7期

机译：芹菜素通过雌激素受体-α依赖性和雌激素受体-α依赖性机制抑制抗雌激素的乳腺癌细胞生长。
4. Assessing the phosphorylation status of estrogen receptor alpha isolated from human breast cancer cells [C] . David J. Britton, Birgit Schilling, Gary K. Scott, ASMS Conference on Mass Spectrometry and Allied Topics . 2007

机译：评估人乳腺癌细胞中雌激素受体α的磷酸化状态
5. SIRT1 represses estrogen-signaling, ligand-independent estrogen receptor alpha-mediated transcription, and cell proliferation in breast cancer cells via inhibition of the phosphoinositide 3-kinases pathway [D] . Moore, Robert L. 2011

机译：SIRT1通过抑制磷酸肌醇3激酶途径抑制雌激素信号传导，配体独立的雌激素受体α介导的转录和乳腺癌细胞的增殖
6. Estrogen receptor alpha 46 is reduced in tamoxifen resistant breast cancer cells and re-expression inhibits cell proliferation and estrogen receptor alpha 66-regulated target gene transcription [O] . Carolyn M. Klinge, Krista A. Riggs, Nalinie S. Wickramasinghe, -1

机译：雌激素受体α46在三莫氧基抗性乳腺癌细胞中降低再表达抑制细胞增殖和雌激素受体α66调节的靶基因转录
7. Estrogen receptor alpha 46 is reduced in tamoxifen resistant breast cancer cells and re-expression inhibits cell proliferation and estrogen receptor alpha 66-regulated target gene transcription [O] . Carolyn M. Klinge, Krista A. Riggs, Nalinie S. Wickramasinghe, 2010

机译：雌激素受体α46在三莫氧基抗性乳腺癌细胞中降低，再表达抑制细胞增殖和雌激素受体α66调节的靶基因转录
8. Membrane Estrogen Receptor Alpha Targeting and its Association with SHC in Regulating Breast Cancer Cell Proliferation [R] . Song, R. X. 2004

机译：膜雌激素受体α靶向及其与sHC调节乳腺癌细胞增殖的关系

Estrogen receptor alpha 46 is reduced in tamoxifen resistant breast cancer cells and re-expression inhibits cell proliferation and estrogen receptor alpha 66-regulated target gene transcription.

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