Potentiation of epidermal growth factor receptor-mediated oncogenesis by c-Src: implications for the etiology of multiple human cancers.

作者: M. C. Maa , T. H. Leu , D. J. McCarley , R. C. Schatzman , S. J. Parsons

DOI: 10.1073/PNAS.92.15.6981

关键词: Cancer researchReceptorERBB3Epidermal growth factor receptorProto-oncogene tyrosine-protein kinase SrcTyrosine kinaseBiologyGrowth factor receptorPhosphorylationCarcinogenesis

摘要: Abstract c-Src is a nontransforming tyrosine kinase that participates in signaling events mediated by variety of polypeptide growth factor receptors, including the epidermal receptor (EGFR). Overexpression and continual ligand stimulation EGFR results morphological transformation cells vitro tumor development vivo. Elevated levels c-Src are found human malignancies, raising question whether can functionally cooperate with during tumorigenesis. To address this issue, we generated c-Src/EGFR double overexpressors compared their proliferative biochemical characteristics to those single control cells. We expressing high receptor, potentiated DNA synthesis, soft agar, formation nude mice. Growth potentiation was associated heterocomplex between activated EGFR, appearance distinct tyrosyl phosphorylation on an enhancement substrate phosphorylation. These findings indicate capable potentiating receptor-mediated tumorigenesis suggest synergism may contribute more aggressive phenotype multiple tumors.

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