Role of HER4 as Differentiation Factor in Breast Cancer

描述(申请者描述)：候选人：建议的研究计划 将探讨HER4作为一种潜在的分化因子在 人类乳腺癌。萨托尔博士将在 在颁奖期间对H.Shelton Earp博士的直接监督将 显著提高她在基础科学方法论方面的发展 独立调查员的成功。萨特博士的长期职业生涯 目标是成为一名学术放射肿瘤学家，能够结合 乳腺癌患者的多学科护理与生物学研究 人类乳腺癌。她的最终目标是确定 人乳腺中的表皮生长因子受体家族 癌症的预后、治疗反应、复发和 开发针对EGFR家族成员的新治疗策略。资金来源 申请的奖励将确保受保护的远离临床的时间 确保进一步的分子实验室培训所需的职责 肿瘤发生研究。 环境：这项提案的支持来自北卡罗来纳州莱恩伯格大学 综合癌症中心和放射肿瘤科。Dr。 在厄普博士的实验室里为Sartor提供了空间，并使用了核心 癌症中心和北卡罗来纳大学乳腺癌孢子中心的设施。支持将 包括项目所需的设备、试剂和消耗品。为这笔资金提供资金 该提案将确保候选人75%的时间将用于 对这项拟议的研究。 研究：我们的初步研究以及其他人的研究表明 激活HER4的配体可以导致分化和减少 人乳腺癌细胞的增殖。然而，HER4尚未得到证实 在区分中起到直接和因果的作用。因此，我们提出一项 利用稳定表达的HER4、EGFR：HER4嵌合体和 显性阴性HER4突变体确定HER4的激活是否会导致 差异化。我们将定义HER4参与的竞赛 差异化信号，特别注意与其他公司的伙伴关系 EGFR家族成员，在EFG家族成员配体影响下的研究 激活了HER4。然后我们将探索下游的信号转导 HER4信号转导通路参与细胞分化。这些调查途径 将有助于我们更多地理解复杂的和批判性的 乳腺癌中重要的EGFR家族成员，并可能导致这一发现 HER4作为一个重要的预后因素和潜在的新靶点 治疗学。

DESCRIPTION (Applicant's Description): Candidate: The proposed research plan will explore the function of HER4 as a potential differentiation factor in human breast cancer. The training that Dr. Sartor will receive under the direct supervision of Dr. H. Shelton Earp during the award period will significantly enhance her development in basic science methodology critical to the success of an independent investigator. Dr. Sartor's long-term career goals are to become an academic radiation oncologist who can combine multidisciplinary breast cancer patient care with a study of the biology of human breast cancer. Her ultimate goal is to determine the significance of the epidermal growth factor receptor family of receptors in human breast cancer with regard to prognosis, treatment response, recurrence, and to develop new therapeutic strategies that target EGFR family members. Funding of the requested award would ensure the protected time away from clinical responsibilities necessary to ensure further lab training in molecular oncogenesis research. Environment: Support from this proposal comes from the UNC Lineberger Comprehensive Cancer Center and the Departrnent of Radiation Oncology. Dr. Sartor is provided space in Dr. Earp's laboratory as well as use of the core facilities of the Cancer Center and the UNC Breast Cancer SPORE. Support will include equipment, reagents, and consumables for the project. Funding of this proposal will ensure that 75 percent of the candidate's time will be devoted to the proposed research. Research: Our preliminary studies, as well as those of others, demonstrate that ligands that activate HER4 can cause differentiation and decrease proliferation of human breast cancer cells. However, HER4 has not been proven to have a direct and causal role in differentiation. Therefore, we propose a series of experiments using stably expressed HER4, EGFR:HER4 chimera and dominant negative HER4 mutants to determine whether activation of HER4 causes differentiation. We will define the contest in which HER4 is involved in a differentiation signal, paying particular attention to partnership with other EGFR family members, studied under the influence of EFG family member ligands which activate HER4. We will then explore the downstream signal transduction pathways of HER4 involved in differentiation. These avenues of investigation of HER4 will help us to understand more about the complex and critically important EGFR family members in breast cancer, and may lead to the discovery of HER4 as an important prognostic factor and potential target for novel therapeutics.