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Bcl-2 overexpression in PhIP-induced colon tumors: cloning of the rat Bcl-2 promoter and characterization of a pathway involving beta-catenin, c-Myc and E2F1.

Authors: Li, Q  Dashwood, WM  Zhong, X  Nakagama, H  Dashwood, RH 
Citation: Li Q, etal., Oncogene. 2007 Sep 13;26(42):6194-202. Epub 2007 Apr 2.
Pubmed: (View Article at PubMed) PMID:17404573
DOI: Full-text: DOI:10.1038/sj.onc.1210438

Beta-catenin/T-cell factor (Tcf) signaling is constitutively active in the majority of human colorectal cancers, and there are accompanying changes in Bcl-2 expression. Similarly, 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP)-induced colon tumors in the rat have increased beta-catenin and elevated Bcl-2. To examine the possible direct transcriptional regulation of rat Bcl-2 by beta-catenin/Tcf, we cloned and characterized the corresponding promoter region and found 70.1% similarity with its human counterpart, BCL2. Bcl-2 promoter activity was increased in response to LiCl and exogenous beta-catenin, including oncogenic mutants of beta-catenin found in PhIP-induced colon tumors. Protein/DNA arrays identified E2F1, but not beta-catenin/Tcf, as interacting most strongly with the rat Bcl-2 promoter. Exogenous E2F1 increased the promoter activity of rat Bcl-2, except in mutants lacking the E2F1 sites. As expected, beta-catenin induced its downstream target c-Myc, as well as E2F1 and Bcl-2, and this was blocked by siRNA to c-Myc or E2F1. These findings suggest an indirect pathway for Bcl-2 over-expression in PhIP-induced colon tumors involving beta-catenin, c-Myc and E2F1.

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CRRD Object Information
CRRD ID: 2293078
Created: 2008-05-08
Species: All species
Last Modified: 2008-05-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.