Article

The Bcl-w promoter is activated by beta-catenin/TCF4 in human colorectal carcinoma cells.

Cancer Research UK Clinical Centre, Cancer Sciences Division, University of Southampton School of Medicine, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK.
Gene (impact factor: 2.34). 01/2009; 432(1-2):112-7. DOI:10.1016/j.gene.2008.12.002 pp.112-7
Source: PubMed

ABSTRACT The antiapoptotic BCL-2 family protein BCL-W is often overexpressed in colorectal carcinoma (CRC) where it correlates with advanced stage and expression of p53. In this work we have analysed the Bcl-w promoter to identify potential regulators of BCL-W expression in CRC cells. The Bcl-w promoter was highly active in cell lines derived from CRC as well as other cancer types. Although expression of p53 and BCL-W correlate in CRC, overexpression of wild type or mutant p53 did not significantly alter Bcl-w promoter activity, and deletion of endogenous p53 did not alter the expression of Bcl-w RNA in HCT116 cells. Promoter deletion analysis lead to the identification of a potential binding site for TCF/LEF factors, obligate binding partners for beta-catenin, a downstream target of the WNT signalling pathway. TCF4 and beta-catenin interacted with the Bcl-w promoter in intact HCT116 cells and mutation of this site significantly decreased promoter activity. The activity of the Bcl-w promoter was increased or decreased, respectively, by overexpression of beta-catenin or dominant negative TCF4. beta-catenin is activated in the majority of CRC and these results suggest that BCL-W may function as a downstream effector of inappropriate WNT/beta-catenin signalling.

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Keywords

antiapoptotic BCL-2 family protein BCL-W
 
BCL-W correlate
 
BCL-W expression
 
Bcl-w promoter
 
Bcl-w promoter activity
 
colorectal carcinoma
 
CRC cells
 
dominant negative TCF4
 
downstream effector
 
downstream target
 
inappropriate WNT/beta-catenin signalling
 
intact HCT116 cells
 
mutant p53
 
obligate binding partners
 
potential binding site
 
potential regulators
 
promoter activity
 
Promoter deletion analysis lead
 
TCF/LEF factors
 
WNT signalling pathway