Altered distribution of β-catenin, and its binding proteins E-cadherin and APC, in ulcerative colitis-related colorectal cancers
Altered distribution of β-catenin, and its binding proteins E-cadherin and APC, in ulcerative colitis-related colorectal cancers
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DOI：
10.1038/modpathol.3880253
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发表时间：
2001-01-01
期刊：
影响因子：
7.5
通讯作者：
Waldman, FM
中科院分区：
文献类型：
--
作者：
Aust, DE;Terdiman, TP;Waldman, FM
β-连环蛋白途径在结肠上皮细胞转录信号和细胞-细胞相互作用中发挥重要作用。β-连环蛋白及其结合蛋白E-钙粘蛋白和腺瘤性息肉病结肠蛋白(APC)的表达改变在散发性结直肠癌中是常见的事件。溃疡性结肠炎(UC)相关癌症起源于慢性炎症领域，因此β-连环蛋白途径的改变可能与散发性癌症不同。为了验证这一假说，采用免疫组织化学方法检测了33例UC相关癌和42例散发性结直肠癌石蜡切片中β-连环蛋白、E-钙粘蛋白和APC的表达和亚细胞定位。尽管β-连环蛋白和E-钙粘附素在正常结肠上皮细胞中的表达主要局限于侧膜，但两组肿瘤组织中这些蛋白的表达总体上从膜性转移到细胞质。与正常上皮相比，两种癌组织中β-catenin的核定位增加，胞浆APC表达减少，UC相关癌中β-catenin的异常表达与E-cadherin改变的关系比在散发性癌中更为密切。相反，在散发性癌症中，β-连环蛋白的异常表达与APC改变的关系比在UC相关的癌症中更密切。这些数据表明，β-连环蛋白途径的改变在UC相关和散发性结直肠癌中都是重要的。然而，在UC相关性和散发性结直肠癌中，β-连环蛋白、E-钙粘蛋白和APC的表达模式的差异表明，这一途径的特异性改变在这两个癌症组中可能不同。
The beta -catenin pathway plays a central role In transcriptional signaling and cell-cell interactions in colonic epithelium. Alterations of the expression of beta -catenin, and its binding partners E-cadherin and the adenomatous polyposis coli protein (APC), are frequent events in sporadic colorectal cancer. Ulcerative colitis (UC)-related cancers originate in a field of chronic inflammation and therefore may have different alterations in the beta -catenin pathway than sporadic cancers. To test this hypothesis, expression and subcellular localization of beta -catenin, E-cadherin, and APC were detected by immunohistochemistry in paraffin sections from 33 UC-related and 42 sporadic colorectal cancers. Although beta -catenin and E-cadherin expression were predominantly limited to the lateral cell membrane in normal colonic epithelium, both tumor groups showed an overall shift from membranous to cytoplasmic expression for these proteins. An increase in nuclear localization of beta -catenin and a decrease in cytoplasmic APC expression also were seen in both cancer groups compared with normal epithelium, Abnormal beta -catenin expression was more closely linked to E-cadherin alterations in UC-related cancers than in sporadic cancers. In contrast, abnormal beta -catenin expression was more closely linked to APC alterations in sporadic cancers than in UC-related cancers. These data suggest that alterations of the beta -catenin pathway are important in both UC-related and sporadic colorectal cancers. However, differences in the expression patterns of beta -catenin, E-cadherin, and APC between UC-related and sporadic colorectal cancers suggest that the specific alterations in this pathway may differ in these two cancer groups.