Dilek Fatma Hüsniye, Topak Nevin, Aktepe Fatma, Sahin Onder, Türel Kadir Serkan, Sahin Dursun Ali, Dilek Osman Nuri
Department of Pathology, School of Medicine, Kocatepe University, Afyonkarahisar, Turkey.
Pathol Res Pract. 2008;204(11):809-15. doi: 10.1016/j.prp.2008.05.010. Epub 2008 Jul 31.
E-cadherin/beta-catenin complex has a critical role in cell-cell adhesion. beta-Catenin is a critical component of the highly conserved Wnt signaling pathway that regulates cell proliferation and differentiation. Wnt signaling leads to the stabilization of cytosolic beta-catenin and to translocation to the nucleus, where it binds with T-cell factor and promotes the transcription and changes in target gene expression, including matrix metalloproteinases. In this study, we analyzed paraffin-embedded specimens from 42 patients with pT3 rectosigmoid cancer for E-cadherin, beta-catenin, and matrix metalloproteinase-7(MMP-7, matrilysin) expression using immunohistochemistry. Seventy-four and 79% of tumors expressed beta-catenin and E-cadherin, respectively. Nuclear expression of beta-catenin was detected only in 26.1% of tumors. Forty-five percent of the rectosigmoid cancers showed strong expression of MMP-7. It was revealed that membranous or cytoplasmic beta-catenin expression was significantly related to E-cadherin and MMP-7 expression. No significant association was seen between E-cadherin, beta-catenin, or MMP-7 expression and some clinicopathologic features. Our results may contribute to the functional interaction between beta-catenin and MMP-7. Further studies on Wnt/beta-catenin and MMP-7 gene activity and protein expression are necessary to better understand the pathogenesis of colorectal carcinoma.
E-钙黏蛋白/β-连环蛋白复合物在细胞间黏附中起关键作用。β-连环蛋白是高度保守的Wnt信号通路的关键组成部分,该通路调节细胞增殖和分化。Wnt信号导致胞质β-连环蛋白稳定并转位至细胞核,在细胞核中它与T细胞因子结合并促进转录以及靶基因表达的变化,包括基质金属蛋白酶。在本研究中,我们使用免疫组织化学分析了42例pT3直肠乙状结肠癌患者石蜡包埋标本中E-钙黏蛋白、β-连环蛋白和基质金属蛋白酶-7(MMP-7,基质溶素)的表达。分别有74%和79%的肿瘤表达β-连环蛋白和E-钙黏蛋白。仅在26.1%的肿瘤中检测到β-连环蛋白的核表达。45%的直肠乙状结肠癌显示MMP-7强表达。结果显示,膜性或细胞质β-连环蛋白表达与E-钙黏蛋白和MMP-7表达显著相关。未发现E-钙黏蛋白、β-连环蛋白或MMP-7表达与某些临床病理特征之间存在显著关联。我们的结果可能有助于β-连环蛋白与MMP-7之间的功能相互作用。有必要进一步研究Wnt/β-连环蛋白和MMP-7基因活性及蛋白表达,以更好地理解结直肠癌的发病机制。