Domon-Dell Claire, Freund Jean-Noël
Institut National de la Santé et de la Recherche Médicale, Unité 381, 3 avenue Molière, 67200, Strasbourg, France.
FEBS Lett. 2002 May 8;518(1-3):83-7. doi: 10.1016/s0014-5793(02)02650-9.
The homeobox gene Cdx1 is a regulator of intestinal epithelial cell proliferation and differentiation. Using a transfection approach, we showed here that the oncogenic activation of the beta-catenin pathway stimulates the endogenous expression of the Cdx1 mRNA as well as the activity of the Cdx1 promoter in cancer cells of the human colon. Reciprocally, the paralogue homeobox gene Cdx2 exerts an inhibitory effect on the basal and on the beta-catenin-stimulated activity of the Cdx1 promoter. The inhibitory effect of CDX2 requires the intact homeodomain. It is not dependent on canonical CDX binding sites in the Cdx1 promoter nor on the cis-elements specifically targeted by the beta-catenin/Tcf complex. We conclude that the oncogenically activated beta-catenin and CDX2 have opposite and independent effects on the Cdx1 homeobox gene.
同源盒基因Cdx1是肠道上皮细胞增殖和分化的调节因子。通过转染方法，我们在此表明，β-连环蛋白途径的致癌激活刺激了人结肠癌细胞中Cdx1 mRNA的内源性表达以及Cdx1启动子的活性。相反，同源盒基因Cdx2的旁系同源物对Cdx1启动子的基础活性和β-连环蛋白刺激的活性具有抑制作用。CDX2的抑制作用需要完整的同源结构域。它不依赖于Cdx1启动子中的经典CDX结合位点，也不依赖于β-连环蛋白/Tcf复合物特异性靶向的顺式元件。我们得出结论，致癌激活的β-连环蛋白和CDX2对Cdx1同源盒基因具有相反且独立的作用。
