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

The Bcl-w promoter is activated by beta-catenin/TCF4 in human colorectal carcinoma cells
The Bcl-w promoter is activated by beta-catenin/TCF4 in human colorectal carcinoma cells
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 ?-catenin, a downstream target of the WNT signalling pathway. TCF4 and ?-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 ?-catenin or dominant negative TCF4. ?-catenin is activated in the majority of CRC and these results suggest that BCL-W may function as a downstream effector of inappropriate WNT/?-catenin signalling.
bcl-w, bcl2l2, ?-catenin, tcf, apoptosis, transcription
0378-1119
112-117
Lapham, Abigail
6ae23bb1-b405-48b1-b63d-e2ce102c2c03
Adams, Jemimah E.
3a43c890-29ff-4cd5-bc38-ed6f05ed16f8
Paterson, Alex
0ef3054b-2fdc-4586-a086-5762d60c9b3e
Lee, Melanie
dc73838e-cb3e-44b8-9a5e-e048449331d5
Brimmell, Matthew
4bb675a5-c3f0-4ddb-ae49-d39257ba79e1
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Lapham, Abigail
6ae23bb1-b405-48b1-b63d-e2ce102c2c03
Adams, Jemimah E.
3a43c890-29ff-4cd5-bc38-ed6f05ed16f8
Paterson, Alex
0ef3054b-2fdc-4586-a086-5762d60c9b3e
Lee, Melanie
dc73838e-cb3e-44b8-9a5e-e048449331d5
Brimmell, Matthew
4bb675a5-c3f0-4ddb-ae49-d39257ba79e1
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394

Lapham, Abigail, Adams, Jemimah E., Paterson, Alex, Lee, Melanie, Brimmell, Matthew and Packham, Graham (2009) The Bcl-w promoter is activated by beta-catenin/TCF4 in human colorectal carcinoma cells. Gene, 432 (1-2), 112-117. (doi:10.1016/j.gene.2008.12.002).

Record type: Article

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 ?-catenin, a downstream target of the WNT signalling pathway. TCF4 and ?-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 ?-catenin or dominant negative TCF4. ?-catenin is activated in the majority of CRC and these results suggest that BCL-W may function as a downstream effector of inappropriate WNT/?-catenin signalling.

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More information

Published date: 1 March 2009
Keywords: bcl-w, bcl2l2, ?-catenin, tcf, apoptosis, transcription

Identifiers

Local EPrints ID: 149447
URI: http://eprints.soton.ac.uk/id/eprint/149447
ISSN: 0378-1119
PURE UUID: 1c0f688e-618d-407a-8503-83e72c17110f
ORCID for Graham Packham: ORCID iD orcid.org/0000-0002-9232-5691

Catalogue record

Date deposited: 04 May 2010 16:03
Last modified: 14 Mar 2024 02:44

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Contributors

Author: Abigail Lapham
Author: Jemimah E. Adams
Author: Alex Paterson
Author: Melanie Lee
Author: Matthew Brimmell
Author: Graham Packham ORCID iD

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