Signal Transduction by EGF Receptor Tyrosine Kinase
Members of the receptor tyrosine kinase family are frequently implicated in experimental models of neoplasia as well as in human cancer. One of the best studied receptor signaling systems from this family is the epidermal growth factor receptor (EGFR). The EGFR is widely expressed in mammals and has been implicated in various stages of embryonic development. Recently, EGFR knockout mice by targeted disruption of exon 1 (Sibilia and Wagner 1995) or exon 2 (Miettinen et al. 1995; Threadgill et al. 1995) of the mouse EGFR gene have been reported. The resulting phenotypes of EGFR-/- embryos or newborns were very similar. Growth retardation and epithelial immaturity were found, with the severity of defects being dependent on the mouse genetic background. These results indicate that the EGFR is of fundamental importance in the regulation of epithelial proliferation and differentiation. Experiments with transgenic mice suggest that an autocrine mechanism involving the EGFR could be expected to play a role in the initiation and/or progression of tumors. Transgenic mice expressing transforming growth factor-α (TGF-α) were reported to develop mammary and hepatocellular carcinoma as well as pancreatic hyperplasia (Jhappan et al. 1990; Sandgreen et al. 1990).
KeywordsEpidermal Growth Factor Receptor Human Epidermal Growth Factor Receptor Epidermal Growth Factor Receptor Gene Epidermal Growth Factor Receptor Tyrosine Kinase erbB Receptor Family
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