Data from <i>p120-Catenin</i> Is Transcriptionally Downregulated by FOXC2 in Non–Small Cell Lung Cancer Cells

Abstract

<div>Abstract<p>p120-catenin (p120ctn) plays a major role in cell adhesion and motility through the regulation of E-cadherin and interaction with RhoGTPase and Rac1. p120ctn is downregulated in several malignancies including non–small cell lung cancer (NSCLC). Here, we investigated transcriptional regulation of p120ctn in NSCLC. We cloned a 1,400-bp amplicon of chromosome 11 from position −1,082 to +320 relative to the transcription start site into a firefly luciferase reporter vector and prepared serial deletion constructs to pinpoint <i>cis</i>-acting elements involved in the regulation of <i>p120ctn.</i> We transfected NSCLC cell lines and immortalized normal human respiratory epithelial cells with the abovementioned constructs. We found reduced <i>p120ctn</i> promoter activity, protein level, and mRNA message in lung cancer cells compared with noncancerous immortalized lung epithelial cells. Serial deletion analysis of <i>p120ctn</i> promoter identified a region between positions +267 and +282, which mediated the transcriptional repression of <i>p120ctn</i>. This region harbored putative binding sites for FOXC2 and FOXL1 transcription factors. Direct binding of FOXC2 to the <i>p120ctn</i> promoter between positions +267 and +282 was confirmed by electromobility shift assay. RNAi-mediated silencing of FOXC2 in A549, H157, and H358 cells resulted in increasing <i>p120ctn</i> promoter activity as well as mRNA and protein levels. Finally, silencing FOXC2 in these NSCLC cells enhanced E-cadherin level, which was reversed by simultaneous silencing of p120ctn. In summary, our data support the notion that FOXC2 mediates the transcriptional repression of <i>p120ctn</i> in NSCLC. Mol Cancer Res; 8(5); 762–74. ©2010 AACR.</p></div>