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论文类型：期刊论文

发表时间：2013-06-07

发表刊物：PLOS ONE

收录刊物：SCIE、PubMed、Scopus

卷号：8

期号：6

页面范围：e65556

ISSN号：1932-6203

摘要：Epithelial Mesenchymal Transition (EMT) plays a major role in cancer metastasis. SevER alpha l genes have been shown to play a role in EMT, and one of these is Amplified-in-breast cancer 1 (AIB1), which has oncogenic function and is known to be amplified in breast cancer. However, the role of AIB1 in EMT remains largely undefined at the molecular level. In this study, the effect of AIB1 overexpression on the EMT of the breast cancer cell line T47D was investigated. Overexpression of AIB1 disrupted the epithelial morphology of the cells. At the same time, the cells displayed a strong metastasis and reduced level of the epithelial marker E-cadherin. In contrast, knockdown of AIB1 in T47D cells increased cell-cell adhesion and produced weak metastasis, as well as a higher level of E-cadherin expression. We proposed that the regulation of EMT by AIB1 occurred through the action of the transcription factor SNAI1, and demonstrated that such interaction required the participation of ER alpha and the presence of ER alpha-binding site on SNAI1 promoter. The expression level of E-cadherin and the extent of cell migration and invasion in SNAI1-knocked down T47D cells that overexpressed AIB1 were similar to those of T47D cells that did not overexpress AIB1 and had no SNAI1 knockdown. Taken together, these results suggested that AIB1 exerted its effect on EMT through its interaction with ER alpha, which could directly bind to the ER alpha-binding site on the SNAI1 promoter, allowing the AIB1-ER alpha complex to promote the transcription of SNAI1 and eventually led to repression of E-cadherin expression, consistent with the loss of E-cadherin being a hallmark of EMT.