DePriest Adam D, Fiandalo Michael V, Schlanger Simon, Heemers Frederike, Mohler James L, Liu Song, Heemers Hannelore V
Department of Cancer Genetics
Department of Urology, Roswell Park Cancer Institute, Buffalo, NY, USA.
Database (Oxford). 2016 Feb 13;2016. doi: 10.1093/database/bav125. Print 2016.
Androgen receptor (AR) is a ligand-activated transcription factor that is the main target for treatment of non-organ-confined prostate cancer (CaP). Failure of life-prolonging AR-targeting androgen deprivation therapy is due to flexibility in steroidogenic pathways that control intracrine androgen levels and variability in the AR transcriptional output. Androgen biosynthesis enzymes, androgen transporters and AR-associated coregulators are attractive novel CaP treatment targets. These proteins, however, are characterized by multiple transcript variants and isoforms, are subject to genomic alterations, and are differentially expressed among CaPs. Determining their therapeutic potential requires evaluation of extensive, diverse datasets that are dispersed over multiple databases, websites and literature reports. Mining and integrating these datasets are cumbersome, time-consuming tasks and provide only snapshots of relevant information. To overcome this impediment to effective, efficient study of AR and potential drug targets, we developed the Regulators of Androgen Action Resource (RAAR), a non-redundant, curated and user-friendly searchable web interface. RAAR centralizes information on gene function, clinical relevance, and resources for 55 genes that encode proteins involved in biosynthesis, metabolism and transport of androgens and for 274 AR-associated coregulator genes. Data in RAAR are organized in two levels: (i) Information pertaining to production of androgens is contained in a 'pre-receptor level' database, and coregulator gene information is provided in a 'post-receptor level' database, and (ii) an 'other resources' database contains links to additional databases that are complementary to and useful to pursue further the information provided in RAAR. For each of its 329 entries, RAAR provides access to more than 20 well-curated publicly available databases, and thus, access to thousands of data points. Hyperlinks provide direct access to gene-specific entries in the respective database(s). RAAR is a novel, freely available resource that provides fast, reliable and easy access to integrated information that is needed to develop alternative CaP therapies. Database URL: http://www.lerner.ccf.org/cancerbio/heemers/RAAR/search/.
雄激素受体(AR)是一种配体激活的转录因子,是治疗非器官局限性前列腺癌(CaP)的主要靶点。延长生命的AR靶向雄激素剥夺疗法失败的原因在于控制内分泌雄激素水平的类固醇生成途径的灵活性以及AR转录输出的变异性。雄激素生物合成酶、雄激素转运蛋白和AR相关共调节因子是有吸引力的新型CaP治疗靶点。然而,这些蛋白质具有多种转录变体和异构体,会发生基因组改变,并且在CaP之间存在差异表达。确定它们的治疗潜力需要评估分散在多个数据库、网站和文献报告中的大量、多样的数据集。挖掘和整合这些数据集是繁琐、耗时的任务,并且只能提供相关信息的快照。为了克服这一阻碍对AR和潜在药物靶点进行有效、高效研究的障碍,我们开发了雄激素作用调节剂资源库(RAAR),这是一个非冗余、经过整理且用户友好的可搜索网络界面。RAAR集中了关于55个编码参与雄激素生物合成、代谢和转运的蛋白质的基因以及274个AR相关共调节因子基因的基因功能、临床相关性和资源信息。RAAR中的数据分为两个层次:(i)与雄激素产生相关的信息包含在一个“受体前水平”数据库中,共调节因子基因信息在一个“受体后水平”数据库中提供,(ii)一个“其他资源”数据库包含指向其他数据库的链接,这些数据库与RAAR中提供的信息互补且有助于进一步探索。对于其329个条目中的每一个,RAAR都提供了对20多个精心整理的公开可用数据库的访问权限,从而可以访问数千个数据点。超链接提供了对各个数据库中特定基因条目的直接访问。RAAR是一种新颖的免费资源,可快速、可靠且轻松地访问开发替代性CaP疗法所需的综合信息。数据库网址:http://www.lerner.ccf.org/cancerbio/heemers/RAAR/search/