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
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
1 March 2009
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), .
(doi:10.1016/j.gene.2008.12.002).
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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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
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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
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