THE ROLE OF EGFR IN UV-INDUCED SKIN CARCINOGENESIS

描述(摘自候选人的摘要) 紫外线辐射(UV)被认为是主要的环境因素 导致非黑色素瘤皮肤癌发生的危险因素 美国高加索人最常见的癌症。紫外线已经被证明是 激活上皮细胞的表皮生长因子受体(EGFR)。 暴露在紫外线下也会导致细胞增殖，表皮增生， 基因启动的v-Ha-ras转基因TG.AC细胞的凋亡与皮肤肿瘤 老鼠。EGFR的激活对角质形成细胞是有丝分裂的，并有助于 皮肤肿瘤在v-Ha-ras启动细胞中的生长。这项提议旨在 验证紫外线诱导的EGFR激活对紫外线有贡献的假设 诱导皮肤肿瘤的发生，表明EGFR信号通路的阻断 预防紫外线引起的皮肤肿瘤的潜力。具体目标1将 确定紫外线是否激活小鼠、人皮肤和角质形成细胞中的EGFR 以及它对v-Ha-ras紫外线诱导的小鼠皮肤乳头状瘤是否有效 转基因TG.AC小鼠。特定的目标2将决定EGFR的激活 紫外线可促进细胞增殖，抑制细胞凋亡 人和小鼠的角质形成细胞和皮肤。具体目标3将决定 LTV诱导的EGFR激活是否参与v-Ha-ras启动的皮肤 肿瘤发生学。

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.