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Title

The transcription factors Slug and Snail act as repressors of Claudin-1 expression in epithelial cells1

AuthorsMartínez-Estrada, Ofelia M.; Peinado, Héctor; Reina, Manuel; Cano, Amparo ; Vilaró, Senén
KeywordsClaudin-1
E-cadherin
Slug
Snail
Issue DateMar-2006
PublisherPortland Press
CitationBiochemical Journal 394(2): 449-457 (2006)
AbstractClaudin-1 is an integral membrane protein component of tight junctions. The Snail family of transcription factors are repressors that play a central role in the epithelial–mesenchymal transition, a process that occurs during cancer progression. Snail and Slug members are direct repressors of E-cadherin and act by binding to the specific E-boxes of its proximal promoter. In the present study, we demonstrate that overexpression of Slug or Snail causes a decrease in transepithelial electrical resistance. Overexpression of Slug and Snail in MDCK (Madin–Darby canine kidney) cells down-regulated Claudin-1 at protein and mRNA levels. In addition, Snail and Slug are able to effectively repress human Claudin-1-driven reporter gene constructs containing the wild-type promoter sequence, but not those with mutations in two proximal E-box elements. We also demonstrate by band-shift assay that Snail and Slug bind to the E-box motifs present in the human Claudin-1 promoter. Moreover, an inverse correlation in the levels of Claudin-1 and Slug transcripts were observed in breast cancer cell lines. E-box elements in the Claudin-1 promoter were found to play a critical negative regulatory role in breast cancer cell lines that expressed low levels of Claudin-1 transcript. Significantly, in invasive human breast tumours, high levels of Snail and Slug correlated with low levels of Claudin-1 expression. Taken together, these results support the hypothesis that Claudin-1 is a direct downstream target gene of Snail family factors in epithelial cells.
Description9 pages, 6 figures.-- et al.
Publisher version (URL)http://www.biochemj.org/bj/394/0449/bj3940449.htm
URIhttp://hdl.handle.net/10261/24838
ISSN0264-6021
Appears in Collections:(IIBM) Artículos
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