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標題: 肝細胞生長因子接受體Met與FocalAdhesionKinase在肺腺癌的臨床意義
The clinical significance of Met and Focal Adhesion Kinase in lung adenocarcinoma
作者: 林淑惠
Lin, Shu-Hui
關鍵字: FAK;c-Met;致癌基因;肺腺癌
出版社: 生命科學院碩士在職專班
Focal adhesion kinase(FAK)是一種存於細胞質中的酪氨酸磷酸化激酶,其具有促進細胞遷移、細胞週期之進行及抵抗細胞凋亡等功能。 c-Met 為肝細胞生長因子接受體(hepatocyte growth factor receptor, HGFR),其與血管新生、細胞移動、細胞生長及細胞分化有關。而FAK的過量表現可與肝細胞生長因子的刺激產生協同作用,導致細胞轉型,共同造成細胞的腫瘤化 (Chan et al., 2002, J. Biol. Chem. 277, 50373-50379)。為進一步探討FAK與c-Met的過量表現在人類肺腺癌的作用,我們收集30個國內肺腺癌病例,以免疫組織化學染色法偵測 c-Met 和 FAK 在肺腺癌腫瘤細胞中的表現,結果發現 c-Met 為100%(30/30)的細胞質強陽性反應,其中有27% (8/30)c-Met 呈現細胞核染色, FAK 則呈現93%(28/30)細胞質強陽性反應。另以國外商品化之肺腺癌組織晶片進行免疫組織化學染色偵測 c-Met 和 FAK ,結果發現 c-Met 為100%(18/18)的細胞質強陽性反應,其中有6%(1/18)c-Met 呈現細胞核染色,而 FAK 則為67%(12/18)細胞質強陽性反應。此外,利用免疫沉澱法結果顯示,在30個配對的肺腺癌細胞中,有27%(8/30)的病例其 FAK 與 c-Met 會相互作用,統計分析發現如此穩定之複合物和肺腺癌腫瘤小於3 cm有顯著的相關性(P<0.05)。綜合以上發現,FAK 與 c-Met 之間的交互作用可能在肺腺癌的早期扮演重要的角色。

Focal adhesion kinase (FAK), a 125 kDa cytoplasmic protein tyrosine kinase, is known to play a central role in the control of cell migration, cell cycle progress, and anti-apoptosis. The c-met proto-oncogene encodes a trans-membrane tyrosine kinase receptor for hepatocyte growth factor/scatter factor, which clearly plays a role in a variety of cellular processes, such as angiogenesis, cell motility, proliferation and cell differentiation. Chan et al. has previously demonstrated that increased expression of FAK renders epithelial cells susceptible to transformation by hepatocyte growth factor stimulation (J. Biol. Chem. 277:50373-50379, 2002). To clarify the role of FAK and c-Met in human lung adenocarcinoma, thirty paraffin embedded specimens of lung adenocarcinoma from Taiwanese patients were examined by immunohistochemistry. Strong cytoplasmic staining of c-Met and FAK was respectively detected in 100% (30/30) and 93% (28/30) specimen. Interestingly, in 27% (8/30) of those, c-Met was also detected in the nucleus. In addition, the results derived from a commercialized tissue array containing specimens from 18 lung adenocarcinoma showed that c-Met and FAK had strong cytoplasmic staining in 100% (18/18) and 67% (12/18) of those specimens, respectively. Nuclear staining of c-Met was found in 6% (1/18) of those. To examine the role of the interaction between FAK and c-Met in lung adenocarcinoma, co-immunoprecipitation of both proteins in the lysates from frozen lung adenocarcinoma biopsy was performed. The interaction was detected in 27% (8/30) biopsy, correlated with tumors smaller than 3 cm (P<0.05). In conclusion, the results suggest that elevated expression of FAK and c-Met and, in particular, their interaction may play important roles in the early stage of the tumorigenesis of lung adenocarcinoma.
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