Marsh Lindsey A, Carrera Samantha, Shandilya Jayasha, Heesom Kate J, Davidson Andrew D, Medler Kathryn F, Roberts Stefan Ge
School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
Department of Biological Sciences, University at Buffalo, Buffalo, NY, USA.
Cell Death Dis. 2017 May 11;8(5):e2771. doi: 10.1038/cddis.2017.179.
Tamoxifen binds to oestrogen receptor α (ERα) to elicit distinct responses that vary by cell/tissue type and status, but the factors that determine these differential effects are unknown. Here we report that the transcriptional corepressor BASP1 interacts with ERα and in breast cancer cells, this interaction is enhanced by tamoxifen. We find that BASP1 acts as a major selectivity factor in the transcriptional response of breast cancer cells to tamoxifen. In all, 40% of the genes that are regulated by tamoxifen in breast cancer cells are BASP1 dependent, including several genes that are associated with tamoxifen resistance. BASP1 elicits tumour-suppressor activity in breast cancer cells and enhances the antitumourigenic effects of tamoxifen treatment. Moreover, BASP1 is expressed in breast cancer tissue and is associated with increased patient survival. Our data have identified BASP1 as an ERα cofactor that has a central role in the transcriptional and antitumourigenic effects of tamoxifen.
他莫昔芬与雌激素受体α（ERα）结合，引发因细胞/组织类型及状态而异的不同反应，但决定这些差异效应的因素尚不清楚。在此，我们报告转录共抑制因子BASP1与ERα相互作用，在乳腺癌细胞中，他莫昔芬可增强这种相互作用。我们发现BASP1在乳腺癌细胞对他莫昔芬的转录反应中起主要选择性因子的作用。在乳腺癌细胞中，受他莫昔芬调控的基因中有40%依赖于BASP1，包括几个与他莫昔芬耐药相关的基因。BASP1在乳腺癌细胞中发挥肿瘤抑制活性，并增强他莫昔芬治疗的抗肿瘤作用。此外，BASP1在乳腺癌组织中表达，且与患者生存率提高相关。我们的数据已确定BASP1为一种ERα辅因子，在他莫昔芬的转录和抗肿瘤作用中起核心作用。
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