Androgen Receptor Functional Analyses by High Throughput Imaging Determination of Ligand, Cell Cycle, and Mutation-Specific Effects 英文参考文献.docVIP

下载本文档

1
0
约7.43万字
约 16页
2017-05-11 发布于上海
举报
版权申诉

Androgen Receptor Functional Analyses by High Throughput Imaging Determination of Ligand, Cell Cycle, and Mutation-Specific Effects 英文参考文献.doc

1、本文档共16页，可阅读全部内容。
2、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
7、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
8、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

Androgen Receptor Functional Analyses by High Throughput Imaging Determination of Ligand, Cell Cycle, and Mutation-Specific Effects 英文参考文献

AndrogenReceptorFunctionalAnalysesbyHigh ThroughputImaging:DeterminationofLigand,Cell Cycle,andMutation-SpecificEffects AdamT.Szafran1,MariaSzwarc1,MarcoMarcelli1,2,MichaelA.Mancini1* 1Departments of Molecular and Cellular Biology and Medicine, Baylor College of Medicine, Houston, Texas, United States of America, 2The Michael E. DeBakey VA MedicalCenter,BaylorCollegeofMedicine,Houston,Texas,UnitedStatesofAmerica Abstract Background:Understandinghowandrogenreceptor(AR)functionismodulatedbyexposuretosteroids,growthfactorsor small molecules can have important mechanistic implications for AR-related disease therapies (e.g., prostate cancer, androgeninsensitivitysyndrome,AIS),andintheanalysisofenvironmentalendocrinedisruptors. Methodology/PrincipalFindings:Wereportthedevelopmentofahighthroughput(HT)image-basedassaythatquantifies ARsubcellularandsubnucleardistribution,andtranscriptionalreportergeneactivityonacell-by-cellbasis.Furthermore, simultaneousanalysisofDNAcontentalloweddeterminationofcellcyclepositionandpermittedtheanalysisofcellcycle dependentchangesinARfunctioninunsynchronizedcellpopulations.AssayqualityforEC50coefficientsofvariationwere 5–24%,withZ’valuesreaching0.91.ThiswasachievedbytheselectiveanalysisofcellsexpressingphysiologicallevelsofAR, important because minor over-expression resulted in elevated nuclear speckling and decreased transcriptional reporter gene activity. A small screen of AR-binding ligands, including known agonists, antagonists, and endocrine disruptors, demonstrated that nuclear translocation and nuclear ‘‘speckling’’ were linked with transcriptional output, and specific ligandswerenotedtodifferentiallyaffectmeasurementsforwildtypeversusmutantAR,suggestingdifferingmechanisms ofaction.HTimagingofpatient-derivedAISmutationsdemonstratedaproof-of-principlepersonalizedmedicineapproach torapidlyidentifyligandscapableofrestoringmultipleARfunctions. Conclusions/Significance:HTimaging-basedmultiplexscreeningwillprovidearapid,systems-levelanalysi