Estrogen receptor-beta and breast cancer: Translating biology into clinical practice

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• 作者：Yuet-Kin Leung^a ; ^b ; ^{ricky.leung@uc.edu} ; Ming-Tsung Lee^a ; Hung-Ming Lam^a ; Pheruza Tarapore^a ; ^b ; Shuk-Mei Ho^a ; ^b ; ^c ; ^d
• 关键词：ER尾 isoforms ; Tumor suppressor ; Post-translational modification ; Extranuclear localization ; Co-regulators ; Phytoestrogen
• 刊名：Steroids
• 出版年：2012
• 期刊代码：142_0039128x
• 类别：bio
• 出版时间：June, 2012
• 卷：77
• 期：7
• 页码：727-737
• 文件大小：635 K

摘要

Estrogen receptor (ER) 尾 was discovered over a decade ago. The design of most studies on this receptor was based on knowledge of its predecessor, ER伪. Although breast cancer (BCa) has been a main focus of ER尾 research, its precise roles in breast carcinogenesis remain elusive. Data from in vitro models have not always matched those from observational or clinical studies. Several inherent factors may contribute to these discrepancies: (a) several ER尾 spliced variants are expressed at the protein level, and isoform-specific antibodies are unavailable for some variants; (b) post-translational modifications of the receptor regulate receptor functions; (c) the role of the receptor differs significantly depending on the type of ligands, cis-elements, and co-regulators that interact with the receptor; and (d) the diversity of distribution of the receptor among intracellular organelles of BCa cells. This review addresses the gaps in knowledge in ER尾 research as it pertains to BCa regarding the following questions: (1) is ER尾 a tumor suppressor in BCa?; (2) do ER尾 isoforms play differential roles in breast carcinogenesis?; (3) do nuclear signaling and extranuclear ER尾 signaling differ in BCa?; (4) what are the consequences of post-translational modifications of ER尾 in BCa?; (5) how do co-regulators and interacting proteins increase functional diversity of ER尾?; and (6) how do the types of ligand and regulatory cis-elements affect the action of ER尾 in BCa?. Insights gained from these key questions in ER尾 research should help in prevention, diagnosis/prognosis, and treatment of BCa.