THE ROLE OF EGFR IN UV-INDUCED SKIN CARCINOGENESIS

描述（摘自候选人摘要） 紫外线辐射（UV）暴露被认为是主要的环境 导致非黑色素瘤皮肤癌发展的危险因素， 美国白人最常见的癌症 紫外线已被证明 激活上皮细胞中的表皮生长因子受体（EGFR）。 暴露于UV也诱导细胞增殖，表皮增生， 基因启动的v-Ha-ras转基因TG.AC中的细胞凋亡和皮肤肿瘤 小鼠 EGFR的活化对角质形成细胞具有促有丝分裂作用，并有助于 v-Ha-ras起始细胞中皮肤肿瘤生长。 这项建议旨在 检验UV诱导的EGFR活化有助于UV- 诱导皮肤肿瘤的发展，这表明阻断EGFR信号传导， 预防紫外线诱导的皮肤肿瘤的潜力。 具体目标1将 确定UV是否激活小鼠和人类皮肤及角质形成细胞中的EGFR 以及它是否在紫外线诱导的小鼠皮肤乳头状瘤中具有活性 转基因TG.AC小鼠。 具体目标2将确定EGFR激活是否 结果增加细胞增殖和抑制细胞凋亡， 人和小鼠角质形成细胞和皮肤。 具体目标3将确定 LTV诱导的EGFR活化是否有助于v-Ha-ras启动的皮肤 肿瘤发生

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.