Expression and mutational analysis of MET in human solid cancers.
Expression and mutational analysis of MET in human solid cancers.
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DOI：
10.1002/gcc.20604
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发表时间：
2008-12
影响因子：
3.7
通讯作者：
Salgia, Ravi
中科院分区：
文献类型：
--
作者：
Ma, Patrick C.;Tretiakova, Maria S.;MacKinnon, Alexander C.;Ramnath, Nithya;Johnson, Candace;Dietrich, Sascha;Seiwert, Tanguy;Christensen, James G.;Jagadeeswaran, Ramasamy;Krausz, Thomas;Vokes, Everett E.;Husain, Aliya N.;Salgia, Ravi
MET受体酪氨酸激酶及其配体肝细胞生长因子（HGF）调节多种细胞功能，其中许多功能在人类癌症中可能失调。活化的MET信号传导可导致细胞运动和分散、血管生成、增殖、分支形态发生、侵袭和最终转移。我们进行了系统的分析MET受体和其配体HGF在肿瘤组织芯片（TMA）从人类实体癌的表达。使用标准免疫组织化学和计算机化自动评分系统。还对非激酶和激酶结构域中的MET突变进行了DNA测序。MET在人实体癌中差异性过表达。配体HGF广泛表达于肿瘤（主要是肿瘤内）和非恶性组织中。MET/HGF可能是功能性的，并且可能在体内以自分泌方式被激活。MET和SCF在肺癌的支气管肺泡连接处呈阳性表达。MET的许多新突变被鉴定，特别是在细胞外信号蛋白结构域和质膜结构域。MET-HGF途径可以在TMA中测定，并且通常在多种人类实体癌中过表达。MET可通过恶性细胞中的过表达、突变或自分泌信号传导而被激活。MET非激酶区的突变可能在肿瘤的发生和发展中起重要作用。MET是一个重要的抗肿瘤治疗靶点，在肺癌中，MET可能代表癌症早期祖细胞标志物。
MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) regulate a variety of cellular functions, many of which can be dysregulated in human cancers. Activated MET signaling can lead to cell motility and scattering, angiogenesis, proliferation, branching morphogenesis, invasion, and eventual metastasis. We performed systematic analysis of the expression of the MET receptor and its ligand HGF in tumor tissue microarrays (TMA) from human solid cancers. Standard immunohistochemistry and a computerized automated scoring system were used. DNA sequencing for MET mutations in both non-kinase and kinase domains was also performed. MET was differentially overexpressed in human solid cancers. The ligand HGF was widely expressed in both tumor, primarily intra-tumoral, and non-malignant tissues. The MET/HGF likely is functional and may be activated in autocrine fashion in vivo. MET and SCF were found to be positively stained in the bronchioalevolar junctions of lung tumors. A number of novel mutations of MET were identified, particularly in the extracellular semaphorin domain and the juxtamembrane domain. MET-HGF pathway can be assayed in TMAs and is often overexpressed in a wide variety of human solid cancers. MET can be activated through overexpression, mutation, or autocrine signaling in malignant cells. Mutations in the non-kinase regions of MET might play important role in tumorigenesis and tumor progression. MET would be an important therapeutic anti-tumor target to be inhibited, and in lung cancer, MET may represent a cancer early progenitor cell marker.
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影响因子：
45.3
作者：
Eberhard, DA;Johnson, BE;Hillan, KJ
通讯作者：
Hillan, KJ
影响因子：
158.5
作者：
Kobayashi, S;Boggon, TJ;Halmos, B
通讯作者：
Halmos, B
影响因子：
11.5
作者：
Ma, PC;Schaefer, E;Salgia, R
通讯作者：
Salgia, R
DOI：
10.1073/pnas.0407651101
发表时间：
2004-12-07
影响因子：
11.1
作者：
Graveel, C;Su, YL;Woude, GV
通讯作者：
Woude, GV
DOI：
10.1073/pnas.0710370104
发表时间：
2007-12-26
影响因子：
11.1
作者：
Bean, James;Brennan, Cameron;Pao, William
通讯作者：
Pao, William