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: 6999282
• 负责人: CAROLYN I SARTOR
• 金额: $ 6.51万
• 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/6999282
• 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：提出的研究计划

项目成果

Mechanism of lapatinib-mediated radiosensitization of breast cancer cells is primarily by inhibition of the Raf>MEK>ERK mitogen-activated protein kinase cascade and radiosensitization of lapatinib-resistant cells restored by direct inhibition of MEK.

• DOI: 10.1016/j.radonc.2009.09.006
• 发表时间: 2009-12
• 期刊: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
• 作者: Sambade MJ;Camp JT;Kimple RJ;Sartor CI;Shields JM
• 通讯作者: Shields JM

Molecular targets as therapeutic strategies in the management of breast cancer.

• DOI: 10.1053/srao.2002.35253
• 发表时间: 2002-10
• 期刊: Seminars in radiation oncology
• 影响因子: 3.5
• 作者: Carolyn I. Sartor

Lapatinib in combination with radiation diminishes tumor regrowth in HER2+ and basal-like/EGFR+ breast tumor xenografts.

• DOI: 10.1016/j.ijrobp.2009.12.063
• 发表时间: 2010-06-01
• 期刊: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
• 影响因子: 7
• 作者: Sambade, Maria J.;Kimple, Randall J.;Camp, J. Terese;Peters, Eldon;Livasy, Chad A.;Sartor, Carolyn I.;Shields, Janiel M.
• 通讯作者: Shields, Janiel M.

Effects of the EGFR/HER2 kinase inhibitor GW572016 on EGFR- and HER2-overexpressing breast cancer cell line proliferation, radiosensitization, and resistance.

• DOI: 10.1016/j.ijrobp.2003.09.046
• 发表时间: 2004-02
• 期刊: International journal of radiation oncology, biology, physics
• 作者: Hong Zhou;Yeon-Shil Kim;Aaron Peletier;Wes McCall;H. Earp;Carolyn I. Sartor