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: 6644875
• 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/6644875
• 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（申请人描述）：候选人：拟议的研究计划 将探索HER4作为一种潜在的分化因子在 人类乳腺癌 Sartor博士将在 H博士的直接监督。 谢尔顿厄普在颁奖期间将 大大促进了她在基础科学方法学方面的发展， 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，能够将联合收割机 多学科乳腺癌患者护理与生物学的研究 人类乳腺癌 她的最终目标是确定 人乳腺表皮生长因子受体家族 癌症的预后，治疗反应，复发， 开发针对EGFR家族成员的新治疗策略。 资金 要求的奖励将确保受保护的时间远离临床 确保进一步的分子实验室培训所需的责任 肿瘤发生研究。 工作环境： 该提案的支持来自于德国莱茵博格大学 综合癌症中心和放射肿瘤学的发展。 博士 萨托在厄普博士的实验室里获得了空间， 癌症中心和乳腺癌中心的设施。 支持将 包括项目所需的设备、试剂和消耗品。 为此提供资金 一份提案将确保候选人75%的时间将用于 所提议的研究。 调研： 我们和其他人的初步研究表明， 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尚未被证实 在分化中有直接的因果作用。 因此，我们建议 使用稳定表达的HER4、EGFR：HER4嵌合体和 显性阴性HER4突变体，以确定HER4的激活是否引起 分化 我们将定义HER4参与的竞赛， 差异化信号，特别注意与其他 EGFR家族成员，在EFG家族成员配体的影响下研究 从而激活HER 4。 然后我们将探索下游信号转导 HER4参与分化的途径。 这些调查途径 将帮助我们更多地了解复杂的，批判性的 乳腺癌中重要的EGFR家族成员，并可能导致发现 HER4作为一个重要的预后因素和新的治疗的潜在靶点， 治疗学