Identification of MYCBP as a beta-catenin/LEF-1 target using DNA microarray analysis.
Abnormal activation of the beta-catenin signaling pathway can cause various types of cancer. Activation of Wnt pathway leads to stabilization of the beta-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 beta-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, RT-PCR and luciferase assay. We suggest that the MYCBP 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.
Jung
Ho-Chul
HC
College of Pharmacy, Chonnam National University, Gwangju, Korea.
Kim
Kwonseop
K
D000256:Adenoviridae / Q000235:genetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000494:pharmacology*; D004247:DNA / Q000235:genetics*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology*; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D051821:Lymphoid Enhancer-Binding Factor 1; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; C116115:MYCBP protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D012313:RNA; D004247:DNA