Identification of MYCBP as a β-catenin/LEF-1 target using DNA microarray analysis

Abnormal activation of the p-catenin signaling pathway can cause various types of cancer. Activation of Wnt pathway leads to stabilization of the P-catenin protein, which results in its translocation to the nucleus and the formation of complexes with lymphoid enhancer factor-1 (LEF-1) and other T-cell factor (TCF) family of transcription factors to affect the transcription of target genes. However, the entrapment pattern of beta-catenin in the nucleus of normal epithelial cells differs from that in colon carcinoma cells. Normal epithelial cells may have different binding partners of p-catenin and LEF-1 compared to tumor cells, which may result in differential expression of target genes. To investigate LEF-1-induced gene expression profiles, we used DNA microarrays to search the alterations of gene expression in normal epithelia versus cancer cells. Here, we reported 10 potential targets genes of beta-catenin/LEF-1. We showed that the expression of c-myc binding protein (MYCBP) in colon carcinoma cells was consistently upregulated by overexpressed LEF-1, which is confirmed by microarray data, RTPCR and luciferase assay. We suggest that the WCBP gene can be a direct target of beta-catenin/LEF-1 pathway through its LEF-1 binding site(s) in the MYCBP promoter, and that MYCBP up-regulation in colon carcinoma cell may play a co-activator role of c-MYC. (c) 2005 Elsevier Inc. All rights reserved.