Twist is a transcriptional repressor of E-cadherin gene expression in breast cancer

被引：287

作者：

Vesuna, Farhad ^{[1
]}

van Diest, Paul ^{[2
]}

Chen, Ji Hshiung ^{[3
]}

Raman, Venu ^{[1
,4
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA

[2] Univ Med Ctr Utrecht, Dept Pathol, NL-3584 CX Utrecht, Netherlands

[3] Tzu Chi Univ, Dept Life Sci, Hualien, Taiwan

[4] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 367卷 / 02期

关键词：

twist; E-cadherin; breast cancer; transcription regulation;

D O I：

10.1016/j.bbrc.2007.11.151

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Twist is a basic helix loop helix protein that plays a role both in human development and in cancer biogenesis. While characterizing the effects of Twist on breast epithelial cell transformation, we identified E-cadherin as a target gene that is down-regulated by Twist. In this study, we demonstrate that Twist can transcriptionally repress E-cadherin in breast cancer cells. Using transient promoter assays, we show that Twist can down-regulate E-cadherin promoter activity by up to two folds. This is further supported by immunoblot analyses which indicates that over-expression of Twist decreases E-cadherin protein levels in breast cancer cell lines. Subsequently, chromatin immunoprecipitation performed on MCF-7/Twist and Hs578 T (high level of endogenous Twist expression) confirmed Twist binding to the E-cadherin promoter. Finally, the functional relevance of this regulation was verified by quantitative real-time PCR and immunohistochemistry on a cohort of breast cancer samples. (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：235 / 241

页数：7

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