The mutationally activated Met receptor mediates motility and metastasis
The mutationally activated Met receptor mediates motility and metastasis
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DOI：
10.1073/pnas.95.24.14417
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发表时间：
1998-11-24
影响因子：
11.1
通讯作者：
Vande Woude, GF
中科院分区：
文献类型：
--
作者：
Jeffers, M;Fiscella, M;Vande Woude, GF
已在人乳头状肾癌中鉴定出Met突变。我们以前已经表明，这些突变失调的酶活性的Met和NIH 3 T3细胞表达突变激活的Met在体外转化和体内致瘤性。在本研究中，我们发现，突变Met诱导Madin-Darby犬肾细胞在体外的运动和NIH 3 T3细胞在体内的实验性转移，和Ras-Raf-MEK-ERK信号通路，这已经牵连到以前的细胞运动和转移，组成性激活的Met突变体。我们还报告说，转基因小鼠窝藏突变激活Met发展转移性乳腺癌。这些数据证实了突变Met分子的致瘤活性，并证明了它们诱导转移表型的能力。
Mutations in Met have been identified in human papillary renal carcinomas. We have shown previously that these mutations deregulate the enzymatic activity of Met and that NIH 3T3 cells expressing mutationally activated Met are transformed in vitro and are tumorigenic in vivo. In the present investigation, we find that mutant Met induces the motility of Madin-Darby canine kidney cells in vitro and experimental metastasis of NIH 3T3 cells in vivo, and that the Ras-Raf-MEK-ERK signaling pathway, which has been implicated previously in cellular motility and metastasis, is constitutively activated by the Met mutants. We also report that transgenic mice harboring mutationally activated Met develop metastatic mammary carcinoma. These data confirm the tumorigenic activity of mutant Met molecules and dem onstrate their ability to induce the metastatic phenotype.