| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2819036 | Gene | 2009 | 6 Pages |
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 β-catenin, a downstream target of the WNT signalling pathway. TCF4 and β-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 β-catenin or dominant negative TCF4. β-catenin is activated in the majority of CRC and these results suggest that BCL-W may function as a downstream effector of inappropriate WNT/β-catenin signalling.
