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Androgen Signaling and Coactivator Regulation in PCA

PCA 中的雄激素信号转导和共激活因子调节

基本信息

批准号：
8448254
负责人：
Hsing-Jien Kung
金额：
$ 29.08万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2015-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8448254
关键词：
Androgen Receptor Androgens Antibodies Arginine Attention Basic Science Binding Sites Biochemical Biological Biological Markers Cancer Biology Castration Cell Cycle Cell Cycle Progression Cell Line Complex Coupled Cyclin A Data Development Disease Enzymes Epidermal Growth Factor Receptor Epigenetic Process Excision Exhibits Family Gene Targeting Genes Genome Growth Growth Factor Health Histone Code Histone Deacetylase Inhibitor Histones Hormones In Vitro Intervention Knowledge Ligand Binding Lysine Malignant neoplasm of prostate Methylation Molecular Monitor Mutation Peptides Pharmaceutical Preparations Play Post-Translational Protein Processing Property Protein Tyrosine Kinase PubMed Publications Published Comment Refractory Regulation Resistance Role Signal Transduction Site Specificity Specimen Substrate Specificity Tail Tissues Transcription Coactivator Transducers Transfection Translational Research Vorinostat Work Xenograft procedure base castration resistant prostate cancer chromatin immunoprecipitation chromatin remodeling clinically significant effective therapy enzyme substrate fascinate histone acetyltransferase in vivo inhibitor/antagonist overexpression progression marker promoter prostate cancer cell prostate carcinogenesis receptor receptor binding receptor expression response small molecule src-Family Kinases therapeutic target tumor

项目摘要

Androgen receptor plays a significant role in prostate carcinogenesis and its overexpression and aberrant activation are considered to be the underlying cause for the development of castration- resistant tumors, which at present defy any effective treatment. As a transcriptional factor, androgen receptor is involved in the assembly of transcriptional complex including coactivators on the target genome site. One special class of coactivators are histone modifying enzymes and the best understood are histone acetylases. A newly emerging class is histone demethylase, which serves to remodel the chromatin surrounding the androgen receptor binding site. They are thus both transcriptional coactivator and epigenetic regulator. The present proposal is based on our identification of a new histone demethylase with all the hallmarks of a strong coactivator of androgen receptor and is overexpressed in prostate cancer. It enhances androgen response, accelerates cell cycle progression, and exhibits a substrate specificity different from the known histone demethylases. Intriguingly, it is regulated by growth factor and is phosphorylated by tyrosine kinases. The enzyme is cell cycle regulated but also regulates cell cycle. Based on these preliminary observations, we wish to elucidate its biochemical properties as a demetylation enzyme, its regulation as a signal transducer, and its biological effects as an androgen receptor coactivator. Its potential as a biomarker and/or a target for therapy will also be evaluated.

雄激素受体在前列腺癌的发生及其过表达中起重要作用