Shen Kang, Yu Huiguang, Xie Baohua, Meng Qiuyu, Dong Chune, Shen Kun, Zhou Hai-Bing
Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Interdisciplinary Research Academy (IRA), Zhejiang Shuren University, Hangzhou 310015, China.
Pharmacol Ther. 2023 Feb;242:108350. doi: 10.1016/j.pharmthera.2023.108350. Epub 2023 Jan 20.
Estrogen receptor β (ERβ) is closely related to breast cancer (BC) progression. Traditional concepts regard ERβ as a tumor suppressor. As studies show the carcinogenic effect of ERβ, some people have come to a new conclusion that ERβ serves as a tumor suppressor in estrogen receptor α (ERα)-positive breast cancer, while it is a carcinogen in ERα-negative breast cancer. However, we re-examine the role of ERβ and find this conclusion to be misleading based on the last decade's research. A large number of studies have shown that ERβ plays an anticancer role in both ERα-positive and ERα-negative breast cancers, and its carcinogenicity does not depend solely on the presence of ERα. Herein, we review the anticancer and oncogenic effects of ERβ on breast cancer progression in the past ten years, discuss the mechanism respectively, analyze the main reasons for the inconsistency and update ERβ selective ligand library. We believe a detailed and continuously updated review will help correct the one-sided understanding of ERβ, promoting ERβ-targeted breast cancer therapy.
雌激素受体β（ERβ）与乳腺癌（BC）进展密切相关。传统观念认为ERβ是一种肿瘤抑制因子。随着研究表明ERβ具有致癌作用，一些人得出了新的结论，即ERβ在雌激素受体α（ERα）阳性乳腺癌中作为肿瘤抑制因子，而在ERα阴性乳腺癌中则是致癌物。然而，基于过去十年的研究，我们重新审视了ERβ的作用，发现这一结论具有误导性。大量研究表明，ERβ在ERα阳性和ERα阴性乳腺癌中均发挥抗癌作用，其致癌性并不完全取决于ERα的存在。在此，我们回顾过去十年ERβ对乳腺癌进展的抗癌和致癌作用，分别讨论其机制，分析不一致的主要原因并更新ERβ选择性配体库。我们相信详细且不断更新的综述将有助于纠正对ERβ的片面理解，推动以ERβ为靶点的乳腺癌治疗。
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