权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular targets of soy isoflavones in breast cancer progression

大豆异黄酮在乳腺癌进展中的分子靶标

基本信息

批准号：
7684814
负责人：
SURANGANIE DHARMAWARDHANE
金额：
$ 11.25万
依托单位：
UNIVERSITY OF PUERTO RICO MED SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-10 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7684814
关键词：
Address Affect Angiogenesis Inhibitors Antibodies Antioxidants Binding Biological Assay Breast Cancer Cell Cancer Patient Cancer cell line Cells Consumption Custom Data Development Dietary Phytochemical Disease Distant Metastasis Estrogen Antagonists Estrogen Receptor beta Estrogen Receptors Estrogens Experimental Designs Fatty acid glycerol esters Focal Adhesion Kinase 1 Genistein Genomics Goals Green Fluorescent Proteins Growth Factor Receptors Guidelines Image Analysis In Situ In Vitro Integrins Knowledge Laboratories Literature Malignant - descriptor Malignant Neoplasms Mammary Neoplasms Mammary gland Mediating Methods Microarray Analysis Molecular Target Mus Neoplasm Metastasis Nude Mice Phosphorylation Phytochemical Post-Translational Protein Processing Prevention Preventive Primary Neoplasm Property Protein Isoforms Proteins Proteomics Public Health Publishing Receptor Signaling Relative (related person)Research Risk Role Signal Pathway Signal Transduction Signaling Molecule Soy Foods Survivors Technology Testing Time Tissue-Specific Gene Expression Transducers Western Blotting Woman base breast tumorigenesis cancer cell cancer initiation carcinogenesis cell motility daidzein design dietary constituent glycitein in vivo innovation malignant breast neoplasm mouse model polyphenol prevent promoter receptor expression response soy soy protein isolate therapeutic target tissue culture tumor tumor growth tumor progression

项目摘要

DESCRIPTION (provided by applicant): The OBJECTIVE of this proposal is to investigate the role of soy phytochemicals, dietary constituents with known cancer-preventive properties, in breast cancer metastasis. The RATIONALE is that soy isoflavones can affect cancer progression by antioxidant, estrogenic/antiestrogenic, antiangiogenic, and other inhibitory mechanisms. Most studies on the role of soy compounds in cancer focus on cancer initiation and not progression. This proposal addresses a GAP IN KNOWLEDGE concerning the molecular targets of the major soy isoflavones genistein and dadizein in breast cancer metastasis, the most deadly aspect of the disease. We have shown that the activity of a key signaling intermediate of cancer cell invasion, focal adhesion kinase (FAK), is regulated by genistein and daidzein in metastatic breast cancer cells. Preliminary data using human breast cancer cells in tissue culture and a nude mouse model of experimental metastasis demonstrate that genistein decreases while daidzein increases metastatic breast cancer cell migration, mammary tumor growth, and metastasis. Our HYPOTHESIS is that genistein prevents while daidzein promotes metastatic breast cancer progression. These differential effects are dependent on the myriad of FAK-mediated signaling cascades. The STUDY DESIGN will use innovative in situ image analysis and genomic and proteomic microarray technology to elucidate the FAK signaling pathways that are regulated differentially by soy isoflavones in metastatic breast cancer cell lines that do not express estrogen receptors (ER), only ER beta or both ER isoforms. AIM 1 will delineate molecular targets of genistein, daidzein, and combined soy isoflavones on metastatic breast cancer cells in vitro. AIM 2 will delineate molecular targets of genistein, daidzein, and combined soy isoflavones on mammary tumors, distant metastases, and invasive breast cancer cells in vivo. The proposed comprehensive-analysis is expected to identify signaling molecules regulated by soy compounds relevant for breast cancer progression. This timely research is SIGNIFICANT to public health by advancing the understanding of the role of natural dietary compounds from soy foods in breast cancer. The proposed elucidation of the specific molecular targets of soy isoflavones will enable targeted therapeutic strategies for metastatic breast cancer. Our broad-range goal is to impact the development of dietary guidelines for women at risk for breast cancer, breast cancer patients, and survivors.

描述（由申请人提供）：本提案的目的是研究大豆植物化学物质（具有已知癌症预防特性的膳食成分）在乳腺癌转移中的作用。依据是大豆异黄酮可以通过抗氧化剂、雌激素/抗雌激素、抗血管生成和其他抑制机制影响癌症进展。大多数关于大豆化合物在癌症中的作用的研究都集中在癌症的发生而不是进展上。这项提案提出了一个知识空白，涉及主要大豆黄酮染料木素和大豆苷元在乳腺癌转移中的分子靶点，乳腺癌转移是疾病最致命的方面。我们已经证明，转移性乳腺癌细胞中，癌细胞侵袭的关键信号中间体，粘着斑激酶（FAK）的活性受染料木素和大豆苷元的调节。使用人乳腺癌细胞在组织培养和裸鼠模型的实验转移的初步数据表明，染料木素减少，而大豆苷元增加转移性乳腺癌细胞迁移，乳腺肿瘤的生长和转移。我们的假设是，染料木黄酮预防，而大豆黄酮促进转移性乳腺癌的进展。这些差异效应依赖于无数的FAK介导的信号级联。研究设计将使用创新的原位图像分析和基因组学和蛋白质组学微阵列技术来阐明FAK信号通路，该通路在不表达雌激素受体（ER）、仅表达ER β或表达两种ER亚型的转移性乳腺癌细胞系中受到大豆异黄酮的差异调节。目的1为探讨染料木黄酮、大豆苷元及联合大豆异黄酮对乳腺癌转移细胞作用的分子靶点奠定基础。目的2将阐明染料木黄酮、大豆苷元和联合大豆异黄酮对乳腺肿瘤、远处转移和浸润性乳腺癌细胞的体内分子靶点。所提出的综合分析，预计将确定信号分子调节的大豆化合物相关的乳腺癌的进展。这项及时的研究通过促进对大豆食品中天然膳食化合物在乳腺癌中作用的了解，对公共卫生具有重要意义。大豆异黄酮的特异性分子靶点的阐明将使转移性乳腺癌的靶向治疗策略成为可能。我们的广泛目标是影响乳腺癌风险女性，乳腺癌患者和幸存者的饮食指南的发展。