Support of a bi-faceted role of estrogen receptor β (ERβ) in ERα-positive breast cancer cells.
Support of a bi-faceted role of estrogen receptor β (ERβ) in ERα-positive breast cancer cells.
复制标题
支持雌激素受体β（ERβ）在ERα阳性乳腺癌细胞中的双重作用。
DOI：
10.1530/erc-13-0444
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发表时间：
2014-04
影响因子：
3.9
通讯作者：
Williams C
中科院分区：
文献类型：
--
作者：
Jonsson P;Katchy A;Williams C
乳腺癌中雌激素受体α（ERα）的表达可以确定最有可能对内分泌治疗产生反应的患者。第二种雌激素受体ERβ也在乳腺肿瘤中表达，但其功能和治疗潜力需要进一步研究。尽管体外研究已证实 ERβ 对抗 ERα 的转录和增殖功能，但一些临床研究报告其与增殖标志物和较差预后的相关性。证明 ERβ 对抗 ERα 的数据主要基于 ERβ 的瞬时表达。在这里，我们探讨了 ERα 阳性乳腺癌细胞系 MCF7 和 T47D 中组成型表达的 ERβ 的功能。我们发现，在存在和不存在 17β-雌二醇的情况下，ERβ 在这些条件下与 ERα 异二聚化，并诱导全基因组转录变化。然而，没有观察到广泛的抗 ERα 信号传导，并且 ERβ 不具有抗增殖作用。在 ERβ 存在和不存在的情况下，他莫昔芬都能拮抗增殖和 ER 介导的基因调控。总之，ERβ 在适应其表达的细胞中的作用似乎不同于其在瞬时表达的细胞中的作用。我们的研究很重要，因为它让我们更深入地了解 ERβ 在共表达两种受体的乳腺肿瘤中的作用，并支持 ERβ 新兴的双向作用。
Expression of estrogen receptor alpha (ERα) in breast cancer identifies patients most likely to respond to endocrine treatment. The second estrogen receptor, ERβ, is also expressed in breast tumors, but its function and therapeutic potential needs further study. Whereas in vitro studies have established that ERβ opposes transcriptional and proliferative functions of ERα, several clinical studies report its correlation to proliferative markers and poorer prognosis. The data demonstrating that ERβ opposes ERα are primarily based on transient expression of ERβ. Here, we explored the functions of constitutively expressed ERβ in ERα-positive breast cancer lines MCF7 and T47D. We found that ERβ, under these conditions heterodimerized with ERα in presence and absence of 17β-estradiol, and induced genome-wide transcriptional changes. Widespread anti-ERα signaling was, however, not observed and ERβ was not anti-proliferative. Tamoxifen antagonized proliferation and ER-mediated gene regulation both in the presence and absence of ERβ. In conclusion, ERβ’s role in cells adapted to its expression appears to differ from its role in cells with transient expression. Our study is important because it provides a deeper understanding of ERβ’s role in breast tumors that co-express both receptors and supports an emerging bi-faceted role of ERβ.