Role of HER4 as Differentiation Factor in Breast Cancer

HER4 作为分化因子在乳腺癌中的作用

• 批准号: 6840523
• 负责人: CAROLYN I SARTOR
• 金额: $ 13.03万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-21 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6840523
• 关键词: biological signal transduction; breast neoplasms; chimeric proteins; enzyme activity; epidermal growth factor; growth factor receptors; heregulin; immunoprecipitation; ligands; mitogen activated protein kinase; mutant; oncoproteins; phosphatidylinositol 3 kinase; protein tyrosine kinase; tissue /cell culture; tumor suppressor proteins

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.

描述（申请人的描述）： 候选人：拟议的研究计划 将探索 HER4 作为潜在分化因子的功能 人类乳腺癌。 Sartor 博士将接受的培训 H. Shelton Earp 博士在颁奖期间的直接监督将 显着增强了她在基础科学方法方面的发展，这对于 独立调查员的成功。 Sartor 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 多学科乳腺癌患者护理与生物学研究 人类乳腺癌。 她的最终目标是确定 人类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 所请求的奖励将确保远离临床的受保护时间 确保进一步的分子实验室培训所必需的责任 肿瘤发生研究。 环境：该提案的支持来自 UNC Lineberger 综合癌症中心和放射肿瘤科。 博士。 为 Sartor 提供了 Earp 博士实验室的空间以及核心的使用 癌症中心和北卡罗来纳大学乳腺癌孢子的设施。 支持会 包括项目的设备、试剂和消耗品。 此项资助 提案将确保候选人 75% 的时间投入 到拟议的研究。 研究：我们的初步研究以及其他人的研究表明 激活 HER4 的配体可以引起分化并减少 人类乳腺癌细胞的增殖。 然而，HER4尚未得到证实 在分化中具有直接和因果作用。 因此，我们提出一个 使用稳定表达的 HER4、EGFR:HER4 嵌合体和 显性失活 HER4 突变体以确定 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，特别注重与其他人的伙伴关系 EGFR 家族成员，在 EFG 家族成员配体的影响下进行研究 从而激活 HER4。 然后我们将探讨下游信号转导 HER4 参与分化的途径。 这些调查途径 HER4 的研究将帮助我们更多地了解复杂且批判性的 乳腺癌中重要的 EGFR 家族成员，并可能导致这一发现 HER4作为重要的预后因素和新药的潜在靶点 疗法。