THE ROLE OF EGFR IN UV-INDUCED SKIN CARCINOGENESIS

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DESCRIPTION (Taken from the Candidate's Abstract) Ultraviolet radiation (UV) exposure is believed to be the major environmental risk factor contributing to the development of non-melanoma skin cancer, the most common cancer in Caucasians in the United States. UV has been shown to activate the epidermal growth factor receptor (EGFR) in epithelial cells. Exposure to UV also induces cell proliferation, epidermal hyperplasia, apoptosis, and skin tumors in genetically-initiated v-Ha-ras transgenic TG.AC mice. Activation of EGFR is mitogenic to keratinocytes and contributes to skin tumor growth in v-Ha-ras initiated cells. This proposal is designed to test the hypothesis that UV-induced activation of EGFR contributes to UV- induced skin tumor development, suggesting that blockade of EGFR signaling has potential for prevention of UV-induced skin tumors. Specific aim 1 will determine whether UV activates EGFR in mouse and human skin and keratinocytes and whether it is active in UV-induced mouse skin papillomas from v-Ha-ras transgenic TG.AC mice. Specific aim 2 will determine whether EGFR activation by UV results in increased cell proliferation and suppression of apoptosis in both human and mouse keratinocytes and skin. Specific aim 3 will determine whether LTV-induced EGFR activation contributes to v-Ha-ras initiated skin tumorigenesis.