EGF acts by binding to EGF receptor (EGFR) on the cell surface and stimulating the intrinsic protein-tyrosine kinase activity of the receptor, and initiates a signal transduction cascade. As a result a variety of biochemical changes take place within the cell, including increased intracellular calcium levels, glycolysis and protein synthesis and transcription of certain genes, which ultimately lead to DNA synthesis and cell proliferation.
Epidermal growth factor receptor (EGFR or ErbB1) is one of four members of the EGF family of type-1 tyrosine kinases, which also includes ErbB2, ErbB3 and ErbB4. EGFR is widely expressed in normal skin epithelial cells. EGFR activation drives cell cycle progression, enhances cell migration, and affects cell differentiation
In general, binding of its ligand, epidermal growth factor (EGF), results in stimulation of the EGFR tyrosine kinase, which in turn stimulates intracellular signal transduction, enhances transcription of growth related genes, and promotes cell growth. In vitro withdrawal of EGF leads to malignant transformation of human breast epithelial cell line HMT- 3522, suggesting that EGF is important in the maintenance of normal cell phenotype. But in some tumor cell lines expressing high levels of EGFR, such as MDA-MB-468 breast cancer cells, EGF stimulation results in a decline in cell adhesion, apoptosis and inhibition of cell proliferation. In A431 epithelial carcinoma, low concentrations of EGF stimulate cell growth, while high concentrations inhibit proliferation in monolayer cultures. EGF is a potential growth stimulator of normal thyroid cells, but inhibits growth of the HTC-TSHr thyroid carcinoma cell line.