Activation of the Met receptor by cell attachment induces and sustains hepatocellular carcinomas in transgenic mice.
Activation of the Met receptor by cell attachment induces and sustains hepatocellular carcinomas in transgenic mice.
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通过细胞附着激活 Met 受体可诱导并维持转基因小鼠的肝细胞癌。
DOI：
10.1083/jcb.153.5.1023
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发表时间：
2001-05-28
影响因子：
7.8
通讯作者：
Bishop, JM
中科院分区：
文献类型：
--
作者：
Wang, R;Ferrell, DL;Faouzi, S;Maher, JJ;Bishop, JM
受体酪氨酸激酶（receptor tyrosine kinases，RTK）的过度表达是人类肿瘤中最常见的异常。推测过表达导致RTK的组成性激活，但该激活的机制尚不确定。在这里，我们表明，过度表达的Met RTK允许激活的受体细胞附着，这种形式的激活可以致瘤。在肝细胞中过表达Met的转基因小鼠发生了肝细胞癌（HCC），这是Met先前涉及的人类肿瘤之一。致瘤性Met通过细胞附着而不是通过配体激活。转基因的失活导致甚至高度晚期肿瘤的消退，这显然是由细胞凋亡和细胞增殖的停止介导的。这些结果揭示了一种以前未被认识到的机制，通过该机制可以介导RTK的致瘤作用，提供了Met可能在HCC的发生和维持中发挥作用的证据，并表明Met可能是过表达受体的肿瘤中的有益治疗靶点。
Overexpression is the most common abnormality of receptor tyrosine kinases (RTKs) in human tumors. It is presumed that overexpression leads to constitutive activation of RTKs, but the mechanism of that activation has been uncertain. Here we show that overexpression of the Met RTK allows activation of the receptor by cell attachment and that this form of activation can be tumorigenic. Transgenic mice that overexpressed Met in hepatocytes developed hepatocellular carcinoma (HCC), one of the human tumors in which Met has been implicated previously. The tumorigenic Met was activated by cell attachment rather than by ligand. Inactivation of the transgene led to regression of even highly advanced tumors, apparently mediated by apoptosis and cessation of cellular proliferation. These results reveal a previously unappreciated mechanism by which the tumorigenic action of RTKs can be mediated, provide evidence that Met may play a role in both the genesis and maintenance of HCC, and suggest that Met may be a beneficial therapeutic target in tumors that overexpress the receptor.
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影响因子：
5.6
作者：
FERRELL, LD;CRAWFORD, JM;NAKANUMA, Y
通讯作者：
NAKANUMA, Y
DOI：
10.1073/pnas.94.25.13868
发表时间：
1997-12-09
影响因子：
11.1
作者：
Giordano, S;Bardelli, A;Comoglio, PM
通讯作者：
Comoglio, PM
DOI：
10.1073/pnas.95.24.14417
发表时间：
1998-11-24
影响因子：
11.1
作者：
Jeffers, M;Fiscella, M;Vande Woude, GF
通讯作者：
Vande Woude, GF
影响因子：
56.9
作者：
BOTTARO, DP;RUBIN, JS;AARONSON, SA
通讯作者：
AARONSON, SA
影响因子：
13.5
作者：
DErrico, A;Fiorentino, M;Grigioni, WF
通讯作者：
Grigioni, WF