Lillehoj Erik P, Lu Wenju, Kiser Timothy, Goldblum Simeon E, Kim K Chul
Department of Pediatrics, University of Maryland School of Medicine, 655 West Baltimore Street, BRB 13-029, Baltimore, MD 21201, USA.
Biochim Biophys Acta. 2007 Jul;1773(7):1028-38. doi: 10.1016/j.bbamcr.2007.04.009. Epub 2007 Apr 22.
beta-Catenin binds to the cytoplasmic region of the type 1 membrane glycoprotein MUC1. In the current study, we utilized HEK293T cells expressing the full-length MUC1 protein, or a CD8/MUC1 fusion protein containing only the MUC1 cytoplasmic tail, to investigate the effects of beta-catenin binding to MUC1 on downstream beta-catenin-dependent events. Compared with HEK293T cells transfected with empty vector or CD8 alone, expression of the MUC1 cytoplasmic tail inhibited beta-catenin binding to E-cadherin, decreased translocation of beta-catenin into the nucleus, reduced activation of the LEF-1 transcription factor, and blocked expression of the cyclin D1 and c-Myc proteins. Furthermore, expression of MUC1 was associated with decreased cell proliferation, either in the context of the transfected HEK293T cells, or when comparing wild type (Muc1(+/+)) vs. knockout (Muc1(-/-)) mouse primary tracheal epithelial cells. We conclude that MUC1 inhibits cell proliferation through a beta-catenin/LEF-1/cyclin D1/c-Myc pathway.
β-连环蛋白与1型膜糖蛋白MUC1的细胞质区域结合。在本研究中，我们利用表达全长MUC1蛋白的HEK293T细胞，或仅包含MUC1细胞质尾的CD8/MUC1融合蛋白，来研究β-连环蛋白与MUC1结合对下游β-连环蛋白依赖性事件的影响。与用空载体或单独的CD8转染的HEK293T细胞相比，MUC1细胞质尾的表达抑制了β-连环蛋白与E-钙黏蛋白的结合，减少了β-连环蛋白向细胞核的转位，降低了LEF-1转录因子的激活，并阻断了细胞周期蛋白D1和c-Myc蛋白的表达。此外，无论是在转染的HEK293T细胞中，还是在比较野生型（Muc1(+/+)）与敲除型（Muc1(-/-)）小鼠原代气管上皮细胞时，MUC1的表达都与细胞增殖减少有关。我们得出结论，MUC1通过β-连环蛋白/LEF-1/细胞周期蛋白D1/c-Myc途径抑制细胞增殖。
