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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >POTENTIATION OF EPIDERMAL GROWTH FACTOR RECEPTOR-MEDIATED ONCOGENESIS BY C-SRC - IMPLICATIONS FOR THE ETIOLOGY OF MULTIPLE HUMAN CANCERS
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POTENTIATION OF EPIDERMAL GROWTH FACTOR RECEPTOR-MEDIATED ONCOGENESIS BY C-SRC - IMPLICATIONS FOR THE ETIOLOGY OF MULTIPLE HUMAN CANCERS

机译：C-SRC对表皮生长因子受体介导的癌发生的增强作用-对多种人类肿瘤的病因学意义

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摘要

c-Src is a nontransforming tyrosine kinase that participates in signaling events mediated by a variety of polypeptide growth factor receptors, including the epidermal growth factor receptor (EGFR). Overexpression and continual ligand stimulation of the EGFR results in morphological transformation of cells in vitro and tumor development in vivo, Elevated levels of c-Src and the EGFR are found in a variety of human malignancies, raising the question of whether c-Src can functionally cooperate with the EGFR during tumorigenesis, To address this issue, we generated c-Src/EGFR double overexpressors and compared their proliferative and biochemical characteristics to those of single overexpressors and control cells, We found that in cells expressing high levels of receptor, c-Src potentiated DNA synthesis, growth in soft agar, and tumor formation in nude mice. Growth potentiation was associated with the formation of a heterocomplex between c-Src and activated EGFR, the appearance of a distinct tyrosyl phosphorylation on the receptor, and an enhancement of receptor substrate phosphorylation, These findings indicate that c-Src is Capable of potentiating receptor-mediated tumorigenesis and suggest that synergism between c-Src and the EGFR may contribute to a more aggressive phenotype in multiple human tumors. [References: 33]
机译：c-Src是一种非转化型酪氨酸激酶，参与由多种多肽生长因子受体（包括表皮生长因子受体（EGFR））介导的信号转导事件。 EGFR的过度表达和持续的配体刺激导致体外细胞形态转变和体内肿瘤发展。在多种人类恶性肿瘤中发现c-Src和EGFR的水平升高，这引发了c-Src是否可以发挥功能的问题在肿瘤发生过程中与EGFR协同作用，为解决此问题，我们生成了c-Src / EGFR双过表达子，并将它们的增殖和生化特性与单个过表达子和对照细胞进行了比较，我们发现在表达高水平受体的细胞中，c- Src增强了DNA合成，在软琼脂中生长以及在裸鼠中形成肿瘤。生长增强作用与c-Src和活化的EGFR之间杂合体的形成，受体上明显的酪氨酰磷酸化的出现以及受体底物磷酸化的增强有关。这些发现表明c-Src有能力增强受体-介导的肿瘤发生，并暗示c-Src与EGFR之间的协同作用可能有助于多种人类肿瘤中更具侵略性的表型。 [参考：33]

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