Expression of Wnt pathway components frizzled and disheveled in colon cancer arising in patients with inflammatory bowel disease.
Expression of Wnt pathway components frizzled and disheveled in colon cancer arising in patients with inflammatory bowel disease.
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DOI：
10.3892/or.18.3.691
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发表时间：
2007-09
期刊：
影响因子：
4.2
通讯作者：
X. You;P. Bryant;F. Jurnak;R. Holcombe
中科院分区：
文献类型：
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作者：
X. You;P. Bryant;F. Jurnak;R. Holcombe
导致Wnt信号通路激活的APC基因突变是散发性结肠癌的一个标志，但在炎症性肠病（IBD）患者发生的结肠癌中很少出现。然而，有证据表明Wnt通路的其他成分在IBD相关结肠癌中可能发生改变。在这项研究中，我们检测了Wnt通路成分卷曲蛋白（Fz，一种细胞表面受体）以及蓬乱蛋白（DVL，一个细胞质信号转导分子家族）在IBD和IBD相关结肠癌中的表达。从有溃疡性结肠炎病史的患者以及散发性结肠癌对照患者获取正常和恶性结肠组织的石蜡切片。用针对Fz1/2受体以及DVL1、DVL2和DVL3的抗体对组织切片进行染色，并通过免疫组织化学观察抗原表达。Fz1/2受体在正常IBD黏膜中极少表达，在IBD结肠癌中不表达，但在癌旁的异型增生组织中强烈表达。DVL1在IBD正常黏膜或非IBD患者的正常黏膜中不表达，但在所有癌症中均表达。DVL2和DVL3在所有检测的正常黏膜样本以及散发性结肠癌中表达，但在IBD患者发生的结肠癌中不表达。本文所报道的IBD组织中Fz和DVL表达的特征为Wnt信号在IBD和IBD相关结肠癌中的重要性，特别是该通路非APC成分的重要性提供了证据。Fz可作为IBD患者异型增生的标志物，DVL1是IBD相关结肠癌的一个潜在治疗靶点。
Mutations in apc which lead to activation of the Wnt signaling pathway are a hallmark of sporadic colon cancers but occur infrequently in colon cancers arising in patients with inflammatory bowel disease (IBD). There is evidence, however, that other components of the Wnt pathway may be altered in IBD-related colon cancer. In this study, we examined the expression the Wnt pathway components frizzled (Fz), the cell surface receptor, and disheveled (DVL), a family of cytoplasmic signal transduction molecules, in IBD and IBD-related colon cancer. Paraffin sections of normal and malignant colon tissues were obtained from patients with a history of ulcerative colitis and from controls with sporadic colon cancer. Tissue sections were stained with antibodies directed against Fz1/2 receptors and DVL1, DVL2 and DVL3 and antigen expression visualized by immunohistochemistry. Fz1/2 receptors were minimally expressed in normal IBD mucosa, were not expressed in IBD colon cancer, but exhibited strong expression in dysplastic tissues adjacent to the cancers. DVL1 was not expressed in IBD normal mucosa or normal mucosa from non-IBD patients, but was expressed in all cancers. DVL2 and DVL3 were expressed in all normal mucosa samples tested, and in sporadic colon cancer, but were not expressed in colon cancers arising in IBD patients. The characteristics of Fz and DVL expression in IBD tissues reported herein provides evidence of the importance of Wnt signaling in IBD and IBD-related colon cancer and, specifically, the significance of non-APC components of this pathway. Fz may serve as a marker for dyspasia in IBD patients and DVL1 is a potential therapeutic target for IBD-related colon cancer.