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目的:探讨整合素αvβ6和钙黏蛋白Fat1在结肠癌中的表达情况,进一步揭示其背后的意义。方法:将100例结肠癌标本的肿瘤边缘部分及肿瘤中心部分制作成200点的组织芯片,用免疫组织化学方法检测整合素αvβ6和钙黏蛋白Fat1在结肠癌不同部位的分布和表达差异。利用siRNA技术和转基因技术对HT-29结肠癌细胞和SW480结肠癌细胞进行试验分组,用流式细胞术检测各组结肠癌细胞表面整合素ανβ6和钙黏蛋白Fat1表达水平;应用Western Blot分析各组结肠癌中Ras蛋白活化的情况。结果:肿瘤侵袭边缘,整合素αvβ6呈现高表达,而钙黏蛋白Fat1低表达;瘤体中央,整合素αvβ6低表达,而钙黏蛋白Fat1高表达。流式细胞分析证实在结肠癌细胞表面,整合素αvβ6和钙黏蛋白Fat1表达水平同样呈现负相关关系。Western Blot分析证实,整合素αvβ6能够促进结肠癌细胞Ras蛋白的活化水平。结论:整合素αvβ6和钙黏蛋白Fat1在结肠癌中呈现负相关表达,αvβ6通过抑制Fat1功能促进Ras蛋白的活化。
OBJECTIVE: To investigate the expression of integrin αvβ6 and cadherin Fat1 in colon cancer and further reveal its significance. METHODS: A total of 200 tissue microarrays were prepared from the tumor margins and the center of the tumor in 100 colon cancer specimens. The distribution and expression differences of integrin αvβ6 and cadherin Fat1 in different parts of colon cancer were detected by immunohistochemistry. The HT-29 colon cancer cells and SW480 colon cancer cells were grouped by siRNA technology and transgenic technology. Flow cytometry was used to detect the expression levels of integrin αvβ6 and cadherin Fat1 on colon cancer cells in each group; Western Blot was used to analyze each group. Ras protein activation in colon cancer. RESULTS: At the edge of tumor invasion, integrin αvβ6 was highly expressed, but cadherin Fat1 was lowly expressed. In the tumor center, integrin αvβ6 was lowly expressed, while cadherin Fat1 was highly expressed. Flow cytometric analysis confirmed that the expression levels of integrin αvβ6 and cadherin Fat1 were also negatively correlated on colon cancer cells. Western Blot analysis confirmed that integrin αvβ6 can promote Ras protein activation in colon cancer cells. CONCLUSION: Integrin αvβ6 and cadherin Fat1 are negatively expressed in colon cancer, and αvβ6 promotes the activation of Ras by inhibiting the function of Fat1.