BCL2L1has a functional role in colorectal cancer and its protein expression is associated with chromosome 20q gain


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Abstract

Colorectal cancer (CRC) is the second leading cause of cancer death in the western world. The majority of CRCs, which develop from adenoma precursor lesions, show gain of chromosome arm 20q, whereBCL2L1is located.BCL2L1is an important apoptosis regulating gene that codes for both an anti-apoptotic (Bcl-xL) and a pro-apoptotic (Bcl-xS) splice variant. The aim of the present study was to investigate whetherBCL2L1contributes to 20q gain-driven colorectal adenoma-to-carcinoma progression. To this end, the functional role ofBCL2L1in cancer-related processes was investigated, and differences inBCL2L1DNA, mRNA, and protein levels were compared between colorectal adenomas and CRCs, as well as between tumours with and without 20q gain. Down-modulation ofBCL2L1inhibited cell viability and anchorage-independent growth of CRC cells, while invasion was not affected.BCL2L1DNA copy number and protein expression were increased in CRCs compared to adenomas (p= 0.00005 andp= 0.03, respectively), while mRNA expression was not. Differences in BCL2L1 protein expression were even more pronounced between tumours with and without 20q gain (p= 0.0001). In conclusion, BCL2L1 is functionally involved in several cancer-related processes and its protein expression is associated with 20q gain. This supports a role for 20q gain-dependent expression of BCL2L1 in colorectal adenoma-to-carcinoma progression. However, the absence of a direct correlation betweenBCL2L1mRNA and protein expression implies that BCL2L1 protein expression is regulated at the post-transcriptional level by a distinct factor on the 20q amplicon (egZNF217, AURKAor miRNAs). Therefore, even thoughBCL2L1affects CRC biology in a 20q gain-dependent manner, it is not likely to be a driver of chromosome 20q gain associated adenoma-to-carcinoma progression. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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