Miyashiro I, Senda T, Matsumine A, Baeg G H, Kuroda T, Shimano T, Miura S, Noda T, Kobayashi S, Monden M
Department of Oncogene Research, Osaka University, Japan.
Oncogene. 1995 Jul 6;11(1):89-96.
Mutations in the APC gene are linked to the development of sporadic colorectal tumors as well as to familial adenomatous polyposis. Recently, the APC protein was reported to associated with catenins, proteins that bind to the cell adhesion molecule E-cadherin. In the present study, we examined the distribution and localization of the APC protein and alpha -catenin in the normal mouse intestine by light and immunoelectron microscopy using specific antibodies. The APC protein was found to be localized in microvilli and in the apical and lateral cytoplasm of the epithelial cells, whereas alpha-catenin was detected only in the lateral cytoplasm. Double-labeling immunoelectron microscopy showed colocalization of the APC protein with alpha-catenin in the lateral cytoplasm, especially along the lateral plasma membrane, although a certain portion of the APC protein in this region was distributed independently of alpha-catenin. These results suggest that a portion of the APC protein localized in the lateral cytoplasm of intestinal epithelial cells functions in cooperation with catenins, whereas the APC protein in microvilli and in the apical cytoplasm has other functions independent of catenins.
APC基因的突变与散发性结直肠肿瘤的发生以及家族性腺瘤性息肉病有关。最近,有报道称APC蛋白与连环蛋白相关,连环蛋白是一种与细胞粘附分子E-钙粘蛋白结合的蛋白质。在本研究中,我们使用特异性抗体,通过光学显微镜和免疫电子显微镜检查了正常小鼠肠道中APC蛋白和α-连环蛋白的分布和定位。发现APC蛋白定位于微绒毛以及上皮细胞的顶端和侧面细胞质中,而α-连环蛋白仅在侧面细胞质中检测到。双标记免疫电子显微镜显示,APC蛋白与α-连环蛋白在侧面细胞质中共定位,尤其是沿着侧面质膜,尽管该区域中一部分APC蛋白独立于α-连环蛋白分布。这些结果表明,定位于肠上皮细胞侧面细胞质中的一部分APC蛋白与连环蛋白协同发挥作用,而微绒毛和顶端细胞质中的APC蛋白具有独立于连环蛋白的其他功能。