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ROLES OF INFLAMMATION AND ANDROGEN METABOLISM IN PROSTATE CANCER DISPARITY

炎症和雄激素代谢在前列腺癌差异中的作用

基本信息

批准号：
8271296
负责人：
RICARDO RICHARDSON
金额：
$ 30.5万
依托单位：
NORTH CAROLINA CENTRAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8271296
关键词：
African American Androgen Metabolism Androgens Apoptotic Arachidonate 5-Lipoxygenase Arachidonic Acids Arrestins Biopsy Specimen Blood CXCL1 gene Caucasians Caucasoid Race Cell Culture Techniques Centers of Research Excellence Clinical Data Development Enzymes Epidermal Growth Factor Epidermal Growth Factor Receptor Excretory function Family Frequencies Gene Expression Regulation Genes Genetic Polymorphism Genotype Glucuronosyltransferase Grant Human IL8 gene IL8RA gene IL8RB gene Individual Inflammation Inflammation Mediators Inflammatory Interleukin 8A Receptor Interleukin-8 Knock-out LTB4R gene Laboratories Leukotriene B4 Lewis Lung Carcinoma Link Malignant neoplasm of prostate Mediating Metabolism Methylation Modeling Molecular Mus National Center on Minority Health and Health Disparities Neoplasm Metastasis Outcome PC3 cell line Pathway interactions Pattern Play Population Production Prostate Prostatic Neoplasms Prostatic Tissue Receptor Signaling Regulation Relative (related person)Role Sampling Small Interfering RNA Testing Testosterone Tissue Sample Tissues Tumor Angiogenesis UGT2B28 UDP-glucuronosyltransferase angiogenesis cancer cell cancer health disparity cancer risk case control chemokine chemokine receptor in vivo leucylarginine men mouse model novel overexpression promoter protein expression receptor receptor expression tumor tumorigenesis

项目摘要

African Americans are >60% more likely to develop and >200% more likely to die from prostate cancer than their Caucasian counterparts. It is known that African Americans are more likely to have inflammation in their prostate biopsy specimens, and tend to have higher levels of androgens in blood than Caucasians. Therefore, we hypothesize that inflammation and androgens metabolism may play critical roles in prostate cancer disparity. We plan to test our hypotheses with the following three Specific Aims: 1) To study whether p-arrestin may contribute to prostate cancer disparity by modulating CXCR2-mediated angiogenesis and metastasis of prostate cancer (PI: Richardson). 2) To determine whether expression and regulation of AloxS and bltl by promoter methylation and polymorphism may contribute to prostate cancer disparity between African American and Caucasian men (PI: Chen). 3) To determine whether polymorphisms of UGT2B genes may contribute to prostate cancer development and disparity (PI: Grant). This project is a multi-Pi and multi-disciplinary study which incorporates expertise of three laboratories to study molecular mechanism of prostate cancer disparity. We expect to define the roles of inflammation and androgen metabolism in prostate cancer disparity.

与非裔美国人相比，非裔美国人患前列腺癌的可能性高60%，死于前列腺癌的可能性高200% 他们的高加索同行。众所周知，非裔美国人更有可能在他们的前列腺活检标本，血液中雄激素水平往往高于高加索人。因此，我们假设炎症和雄激素代谢可能在前列腺中起关键作用。癌症差异。我们计划通过以下三个具体目标来检验我们的假设： 1)研究p-arrestin是否可能通过调节CXCR2介导的前列腺癌的血管生成和转移(PI：Richardson)。 2)确定AloxS和blt1的表达和调控是否通过启动子甲基化和基因多态性可能导致非裔美国人和高加索男性前列腺癌的差异 (Pi：Chen)。 3)确定UGT2B基因的多态是否与前列腺癌的发生有关和差异(PI：Grant)。该项目是一项多PI和多学科的研究，它结合了三个实验室的专业知识研究前列腺癌差异的分子机制。我们希望定义炎症和雄激素代谢在前列腺癌中的差异。