Immunohistochemical analyses of focal adhesion kinase expression in benign and malignant human breast and colon tissues: correlation with preinvasive and invasive phenotypes.
Immunohistochemical analyses of focal adhesion kinase expression in benign and malignant human breast and colon tissues: correlation with preinvasive and invasive phenotypes.
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发表时间：
2000-06
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通讯作者：
W. Cance;Janet E. Harris;M. Iacocca;Elizabeth Roche;Xihui Yang;J. Chang;S. Simkins;LiHui Xu
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作者：
W. Cance;Janet E. Harris;M. Iacocca;Elizabeth Roche;Xihui Yang;J. Chang;S. Simkins;LiHui Xu
粘着斑激酶(FAK)是一种蛋白酪氨酸激酶，与细胞和细胞外基质之间的信号传递有关。蛋白质印迹水平的研究表明FAK在浸润性乳腺癌和结肠癌中表达上调。为了在细胞水平上评估p125FAK的表达，我们开发了能够在福尔马林固定、石蜡包埋的组织切片中特异性检测FAK的单抗，并分析了FAK在人乳腺和结肠组织中的表达水平。免疫荧光分析显示，单抗4.47对BT-474乳腺癌细胞有FAK特异的焦点黏附染色，并通过免疫印迹和免疫沉淀分析检测到MR 125,000蛋白。应用免疫组织化学技术，对36例正常人和43例浸润性或侵袭性乳腺、结肠组织中p125FAK的表达进行了分析。FAK在大多数乳腺良性上皮中弱表达，而在18例浸润性乳腺癌中有14例呈中度或强阳性表达。在7例导管原位癌标本中，FAK呈高表达。FAK在正常结肠上皮细胞中呈交界性或弱阳性表达。在浸润性结肠癌中，FAK在15个肿瘤中有13个呈中等或强阳性表达。此外，FAK在发育不良、癌前病变的结肠上皮区表达上调。这些结果首次在细胞水平上提供了FAK在乳腺癌和结肠癌中可变地过度表达的证据，并表明上调发生在肿瘤形成的早期阶段。
The focal adhesion kinase (FAK) is a protein tyrosine kinase linked to signaling events between cells and the extracellular matrix. Studies at the Western blot level have demonstrated up-regulation of FAK expression in invasive breast and colon cancers. To assess p125FAK expression at the cellular level, we developed monoclonal antibodies that specifically detected FAK in formalin-fixed, paraffin-embedded tissue sections and analyzed the levels of FAK expression in human breast and colon tissues. Monoclonal antibody 4.47 demonstrated FAK-specific focal adhesion staining by immunofluorescence assays on BT-474 breast cancer cells and detected a Mr 125,000 protein by both Western blotting and immunoprecipitation analyses. Using immunohistochemical techniques, the expression of p125FAK was analyzed in 36 normal and 43 preinvasive or invasive human breast and colon tissues from individual patients. FAK was weakly expressed in most benign breast epithelium but was up-regulated at moderate or strong levels in 14 of 18 invasive breast carcinomas. In seven samples of ductal carcinoma-in situ, FAK was overexpressed. Borderline-to-weak expression of FAK was detected in the normal colonic epithelium. In the invasive colon cancers, FAK was overexpressed at moderate or strong levels in 13 of 15 tumors. Furthermore, FAK expression was up-regulated in areas of dysplastic, premalignant colon epithelium. These results provide the first evidence at the cellular level that FAK expression is variably overexpressed in breast and colon cancer and suggest that up-regulation occurs at an early stage of tumorigenesis.