Erythropoietin receptor-driven tumor initiation and progression

项目总结/摘要 了解环境致癌物和肿瘤促进剂如何增加癌症风险的大部分努力 重点关注它们对直接暴露细胞的影响，并确定了局部操作机制 是暴露组织的内源性物质在拟议的研究中，我们将验证红细胞生成素 (EPO)和EPO受体（EPOR）介导对致癌物和肿瘤促进剂的生理反应， 内分泌样机制，并有助于肿瘤的发生和发展。我们研究的目的是 了解致癌和促肿瘤环境因子如何诱导EPO和EPOR表达， EPOR是否在癌前细胞和已形成的肿瘤中表达，在肿瘤的发生发展中起重要作用。 形成和转移进展，以及什么样的分子信号控制非红系细胞中EPOR的表达， EPO在肿瘤发生过程中的靶细胞。为达致这个目标，我们会致力达致以下的具体目标： 确定表皮EPOR在皮肤癌发生中的作用（目标#1）;确定黑色素瘤的作用- 在肿瘤生长和转移中表达EPOR（目的#2）;为了确定EPOR诱导的机制， 肿瘤前体和已建立的肿瘤（目标#3）。从我们的研究中获得的信息不仅会促进 我们对皮肤癌的病原体如何增加肿瘤形成和恶性肿瘤发生率的理解， 而且还揭示了内源性产生的EPO和非红系EPOR在 癌症发展我们希望我们的发现最终能帮助设计出治疗癌症的新策略 预防和管理。

PROJECT SUMMARY/ABSTRACT Most efforts to understand how environmental carcinogens and tumor-promoting agents increase cancer risk have focused on their effects on directly exposed cells and have identified locally operating mechanisms endogenous to the exposed tissue. In the proposed study, we will verify the hypothesis that erythropoietin (EPO) and EPO receptor (EPOR) mediate physiological responses to carcinogens and tumor promoters via endocrine-like mechanisms and contribute to tumor initiation and progression. The goal of our study is to understand how carcinogenic and tumor-promoting environmental agents induce EPO and EPOR expression, whether EPOR expressed in preneoplastic cells and established tumors plays an important role in tumor formation and metastatic progression, and what molecular signals govern EPOR expression in non-erythroid EPO target cells during tumorigenesis. To achieve this goal, we will pursue the following specific aims: To determine the role of epidermal EPOR in skin carcinogenesis (Aim #1); To determine the role of melanoma- expressed EPOR in tumor growth and metastasis (Aim #2); To identify the mechanisms of EPOR induction in tumor precursors and established tumors (Aim #3). Information obtained from our study will not only advance our understanding of how etiologic agents of skin cancer increase the rate of tumor formation and malignant conversion but also shed new light on the role of endogenously produced EPO and non-erythroid EPOR in cancer development. We expect that our findings will ultimately help devise new strategies for cancer prevention and management.