DECREASED EXPRESSION OF MAC-2 (CARBOHYDRATE BINDING PROTEIN-35) AND LOSS OF ITS NUCLEAR-LOCALIZATION ARE ASSOCIATED WITH THE NEOPLASTIC PROGRESSION OF COLON-CARCINOMA
DECREASED EXPRESSION OF MAC-2 (CARBOHYDRATE BINDING PROTEIN-35) AND LOSS OF ITS NUCLEAR-LOCALIZATION ARE ASSOCIATED WITH THE NEOPLASTIC PROGRESSION OF COLON-CARCINOMA
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DOI：
10.1073/pnas.90.8.3466
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发表时间：
1993-04-15
影响因子：
11.1
通讯作者：
MERCURIO, AM
中科院分区：
文献类型：
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作者：
LOTZ, MM;ANDREWS, CW;MERCURIO, AM
Mac-2 凝集素（碳水化合物结合蛋白 35）是一种可溶性 32 至 35 kDa 磷蛋白，可结合含半乳糖的糖复合物。我们在此报告，基于人体组织标本的免疫组织化学，结肠上皮是 Mac-2 体内表达的主要部位。在该上皮中，隐窝底部的增殖细胞不表达 Mac-2，但其表达随着沿隐窝到表面轴的分化而增加。 Mac-2 表达集中在这些分化的上皮细胞的细胞核中。从正常粘膜到腺瘤再到癌的进展与 Mac-2 核定位和表达的显着变化相关。在所有检查的腺瘤 (9/9) 和癌 (13/13) 中，Mac-2 不存在于细胞核中，而是位于细胞质中。对正常粘膜和癌组织的 Mac-2 cDNA 进行测序，结果显示没有特定的突变可以解释这种核定位的丧失。我们还观察到，与正常粘膜相比，癌症中 Mac-2 mRNA 水平降低了 5 至 10 倍，并且 Mac-2 蛋白表达量显着降低。这些观察结果表明Mac-2从细胞核中排除及其表达减少可能与结肠癌的肿瘤进展有关。
The Mac-2 lectin (carbohydrate binding protein 35) is a soluble, 32- to 35-kDa phosphoprotein that binds galactose-containing glycoconjugates. We report here that the colonic epithelium is a major site of Mac-2 expression in vivo based on immunohistochemistry of human tissue specimens. In this epithelium, proliferating cells at the base of the crypts do not express Mac-2 but its expression increases with differentiation along the crypt-to-surface axis. Mac-2 expression is concentrated in the nuclei of these differentiated epithelial cells. The progression from normal mucosa to adenoma to carcinoma is associated with significant changes in Mac-2 nuclear localization and expression. In all adenomas (9/9) and carcinomas (13/13) examined, Mac-2 was not present in the nucleus but was localized in the cytoplasm. Sequencing of Mac-2 cDNAs from normal mucosa and carcinoma revealed no specific mutations that could account for this loss of nuclear localization. We also observed a 5- to 10-fold decrease in Mac-2 mRNA levels in cancer compared to normal mucosa as well as a significant reduction in the amount of Mac-2 protein expressed. These observations suggest that Mac-2 exclusion from the nucleus and its decreased expression may be related to the neoplastic progression of colon cancer.