HGF signaling in African-American and Basal-like Breast Cancer

非裔美国人乳腺癌和基底样乳腺癌中的 HGF 信号传导

基本信息

批准号：
8491064
负责人：
Jodie Michelle Fleming
金额：
$ 19.71万
依托单位：
NORTH CAROLINA CENTRAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8491064
关键词：
Acinus organ component Address African African American Antibodies Behavior Biological Biological Assay Biological Models Breast Breast Cancer Cell Breast Cancer Model Breast Carcinoma Cancerous Caucasians Caucasoid Race Cell Line Cells Characteristics Coculture Techniques Collaborations Data Development Epidemiologic Studies Exposure to Fibroblasts Gene Expression Gene Expression Profile Genes Goals High Prevalence Hospitals Immunohistochemistry In Vitro Incidence Lead Learning Lesion Link Liver Fibrosis Malignant Neoplasms Mammary Gland Parenchyma Mammary Neoplasms Measures Methods Microarray Analysis Modeling Molecular Molecular Profiling Molecular Target Normal tissue morphology Observational Study Pathway interactions Patients Phenotype Play Premenopause Prevention Proteins Proteomics Race Regulation Research Resources Risk Role Signal Pathway Signal Transduction Site Solid Neoplasm Specimen Statistical Models Testing Tissues Tumor Biology Up-Regulation Variant Western Blotting Woman Work base cancer cell cancer health disparity caucasian American cell behavior cell motility cytokine hormone metabolism inhibitor/antagonist insight malignant breast neoplasm migration mortality neoplastic cell novel overexpression paracrine programs protein expression public health relevance research study small hairpin RNA social triple-negative invasive breast carcinoma tumor tumor microenvironment tumor progression

项目摘要

DESCRIPTION (provided by applicant): Premenopausal African-American women suffer disproportionately from a higher incidence of the basal-like "triple-negative" breast cancer compared to Caucasian-American patients. Currently, no effective molecular therapies exist for this highly aggressive cancer and, consequently, patient survival is poor. The majority of studies investigating differences in breast cancer between African- and Caucasian-American women examine tumor characteristics, however, the etiologic factors that lead to this disparity remain undefined. Our preliminary data implicate a role for HGF in breast cancer progression and in differences between African-American and Caucasian patients. To further understand the role of this pathway in cancer disparities we will address two Aims. Aim 1 will identify a gene expression signature for HGF via microarray analysis and use this signature to evaluate the expression of the HGF pathway in African-American vs. Caucasian patients and according to breast cancer subtype. Aim 2 will use primary cell lines from African- American and Caucasian patients to evaluate the effects of variation in HGF expression by fibroblasts on cancer cell phenotypes including proliferation and motility assays. Thus, our primary objective is to identify the mechanisms involved in the development of aggressive, metastatic breast cancer in premenopausal African-Americans, as a consequence of stromal effects at the site of the cancerous lesion. Our team has established research partnerships that provide access to resources including the Normal Breast Study: a unique epidemiologic study of normal tissue from ethnically diverse patients at UNC Hospitals. There are several important biological implications of this work. Tumor biology often takes advantage of existing normal tissue programs. By studying the cancer-adjacent tissue, in combination with tissue adjacent to tumor, we will learn which normal programs the tumor utilizes for progression, and these pathways may be targetable. The observation that the normal breast tissue of African-American women is enriched with proteins from programs distinct from Caucasian women, and that African-American women are predisposed to develop basal-like breast cancer strongly suggests a biological link between race and cancer subtype. The role of differentially regulated stromal-derived proteins in the tumor microenvironment will provide novel insights into the biological basis of racial disparities. The long-term goal of the Fleming-Troester collaboration is to understand tumor-microenvironment interactions and their influence on breast cancer disparities.

描述（由申请人提供）：与高加索裔美国人的患者相比，非裔美国裔美国妇女遭受了更高的基础样“三阴性”乳腺癌发病率的不成比例。目前，这种高度侵略性的癌症尚无有效的分子疗法，因此患者的生存率很差。大多数研究研究了非洲和高加索裔美国人妇女之间乳腺癌差异的研究，但是，导致这种差异的病因学因素仍然不确定。我们的初步数据暗示了HGF在乳腺癌进展中的作用以及非裔美国人和高加索患者之间的差异。为了进一步了解该途径在癌症差异中的作用，我们将解决两个目标。 AIM 1将通过微阵列分析确定HGF的基因表达签名，并使用此签名来评估非裔美国人与高加索患者中HGF途径的表达，并根据乳腺癌亚型评估。 AIM 2将使用非裔美国人和高加索患者的原发性细胞系来评估成纤维细胞对HGF表达变异的影响，包括癌细胞表型，包括增殖和运动性测定。因此，我们的主要目标是确定在癌变部位的基质作用而导致的绝经大型非裔美国人侵袭性，转移性乳腺癌的机制。我们的团队建立了研究合作伙伴关系，可提供对资源的访问，包括正常的乳房研究：来自UNC医院的种族多样性患者的正常组织的独特流行病学研究。这项工作有几种重要的生物学含义。肿瘤生物学通常会利用现有的正常组织程序。通过研究癌症的组织组织，结合与肿瘤相邻的组织结合使用，我们将学习肿瘤用于进展的正常程序，这些途径可能是针对性的。这一观察结果表明，非裔美国人妇女的正常乳房组织富含来自白人妇女的计划的蛋白质，并且倾向于发展非洲裔美国妇女来发展基础类乳腺癌，这强烈建议种族与癌症亚型之间的生物学联系。差异调节的基质衍生蛋白在肿瘤微环境中的作用将为种族差异的生物学基础提供新的见解。 Fleming-Troester合作的长期目标是了解肿瘤 - 微环境相互作用及其对乳腺癌差异的影响。