Jung Ho-Chul, Kim Kwonseop
College of Pharmacy, Chonnam National University, Gwangju, Korea.
Life Sci. 2005 Jul 29;77(11):1249-62. doi: 10.1016/j.lfs.2005.02.009.
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.
β-连环蛋白信号通路的异常激活可导致多种类型的癌症。Wnt通路的激活会导致β-连环蛋白的稳定，进而使其易位至细胞核，并与淋巴样增强因子-1（LEF-1）及其他转录因子T细胞因子（TCF）家族形成复合物，从而影响靶基因的转录。然而，正常上皮细胞核中β-连环蛋白的截留模式与结肠癌细胞中的不同。与肿瘤细胞相比，正常上皮细胞中β-连环蛋白和LEF-1可能具有不同的结合伙伴，这可能导致靶基因的差异表达。为了研究LEF-1诱导的基因表达谱，我们使用DNA微阵列来探寻正常上皮细胞与癌细胞中基因表达的变化。在此，我们报告了β-连环蛋白/LEF-1的10个潜在靶基因。我们发现，在结肠癌细胞中，过表达的LEF-1可使c-myc结合蛋白（MYCBP）的表达持续上调，这一点通过微阵列数据、逆转录-聚合酶链反应（RT-PCR）和荧光素酶测定得到了证实。我们认为，MYCBP基因可通过其启动子中的LEF-1结合位点成为β-连环蛋白/LEF-1通路的直接靶标，且结肠癌细胞中MYCBP的上调可能发挥c-MYC的共激活因子作用。
