Dataset Information


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.

ABSTRACT: 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.

PROVIDER: S-EPMC2267879 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC3148807 | BioStudies
| E-SMDB-1723 | BioStudies
| E-GEOD-3282 | BioStudies
| S-EPMC2920641 | BioStudies
| S-EPMC2150773 | BioStudies
2005-09-02 | E-SMDB-1723 | ArrayExpress
| S-EPMC3114416 | BioStudies
2005-09-10 | E-GEOD-3282 | ArrayExpress
| S-EPMC2812568 | BioStudies
| S-EPMC2806753 | BioStudies