RADIATION-INDUCED AUTOPHOSPHORYLATION OF EPIDERMAL GROWTH-FACTOR RECEPTOR IN HUMAN-MALIGNANT MAMMARY AND SQUAMOUS EPITHELIAL-CELLS

In an effort to identify events initiating up-regulation of epidermal growth factor receptor after single and repeated radiation exposures, we investigated the role of epidermal growth factor receptor, a recept or protein tyrosine kinase, in radiation-induced signal transduction. Human malignant mammary, MCF-7, and squamous, A431, cells showed low b aseline phospho-tyrosine levels of epidermal growth factor receptor, p ermitting reproducible dose-dependent stimulation of epidermal growth factor receptor autophosphorylation after exposure to epidermal growth factor. MCF-7 cells exhibited a mean 2.3-fold increase (95% confidenc e interval: 1.91, 2.65; P < 0.0001) in levels of epidermal growth fact or phosphorylation in response to exposures of 2 Gy, which was substan tially less than the epidermal growth factor receptor Y phosphorylatio n induced by epidermal growth factor. A quantitatively similar radiati on response was seen in A431 cells. In the dose range of 1 to 4 Gy, no clear dose response was seen. There was a rapid induction of radiatio n-induced epidermal growth factor receptor Y phosphorylation, starting within 2 min, with maximum values between 0.5 and 5 min after radiati on exposure followed by a slower decline to baseline levels after 20 m in. The data presented identify the epidermal growth factor receptor p rotein tyrosine kinase associated with the plasma membrane as one targ et for ionizing radiation in the dose range used in radiotherapy. (C) 1996 by Radiation Research Society