Phosphorylation of human estrogen receptor-beta at serine 105 inhibits breast cancer cell migration and invasion

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• 作者：Hung-Ming Lam^a ; C.V. Suresh Babu^a ; Jiang Wang^b ; Yong Yuan^a ; Ying-Wai Lam^a ; ^c ; Shuk-Mei Ho^a ; ^c ; ^d ; ^e ; ^{shuk-mei.ho@uc.edu} ; Yuet-Kin Leung^a ; ^c ; ^d ; ^{ricky.leung@uc.edu}
• 关键词：Phosphorylation ; Estrogen receptor-beta isoforms ; Phospho-mimetics ; Breast cancer ; Invasion ; Migration
• 刊名：Molecular and Cellular Endocrinology
• 出版年：2012
• 期刊代码：109_03037207
• 类别：bio
• 出版时间：6 July, 2012
• 卷：358
• 期：1
• 页码：27-35
• 文件大小：1653 K

摘要

Multiple phosphorylation sites on the human estrogen receptor (hER)伪 were identified and shown to influence mammary carcinogenesis. In contrast, functional phosphorylation sites of hER尾 have yet to be experimentally identified and validated. Here, using mass spectrometry, we uncovered three serines (S75, S87, and S105) in the N-terminus of hER尾 as targets of ERK1/2 and p38 kinases. We raised a specific antibody against phosphorylated S105 (pS105) and demonstrated that this site was endogenously phosphorylated in MDA-MB-231 and BT-474 cells. A phospho-mimetic mutant generated from hER尾1 was found to exhibit higher transactivation activity than hER尾1. Ectopic expression of this mutant inhibited cell migration and invasion, but did not affect cell growth and cell-cycle progression in these cell models. In breast cancer specimens, pS105-hER尾 immunoreactivity was detected with a higher prevalence and intensity than that of hER尾1. These results underscore the functional importance of the first experimentally identified hER尾-phosphorylation site in breast cancer.