{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361699995389521152.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1158/1078-0432.ccr-14-1108"}},{"identifier":{"@type":"URI","@value":"https://aacrjournals.org/clincancerres/article-pdf/21/7/1675/2030047/1675.pdf"}},{"identifier":{"@type":"PMID","@value":"25687267"}}],"dc:title":[{"@value":"Generation 2.5 Antisense Oligonucleotides Targeting the Androgen Receptor and Its Splice Variants Suppress Enzalutamide-Resistant Prostate Cancer Cell Growth"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title>\n                  <jats:p>Purpose: Enzalutamide (ENZ) is a potent androgen receptor (AR) antagonist with activity in castration-resistant prostate cancer (CRPC); however, progression to ENZ-resistant (ENZ-R) CRPC frequently occurs with rising serum PSA levels, implicating AR full-length (ARFL) or variants (AR-Vs) in disease progression.</jats:p>\n                  <jats:p>Experimental Design: To define functional roles of ARFL and AR-Vs in ENZ-R CRPC, we designed 3 antisense oligonucleotides (ASO) targeting exon-1, intron-1, and exon-8 in AR pre-mRNA to knockdown ARFL alone or with AR-Vs, and examined their effects in three CRPC cell lines and patient-derived xenografts.</jats:p>\n                  <jats:p>Results: ENZ-R-LNCaP cells express high levels of both ARFL and AR-V7 compared with CRPC-LNCaP; in particular, ARFL levels were approximately 12-fold higher than AR-V7. Both ARFL and AR-V7 are highly expressed in the nuclear fractions of ENZ-R-LNCaP cells even in the absence of exogenous androgens. In ENZ-R-LNCaP cells, knockdown of ARFL alone, or ARFL plus AR-Vs, similarly induced apoptosis, suppressed cell growth and AR-regulated gene expression, and delayed tumor growth in vivo. In 22Rv1 cells that are inherently ENZ-resistant, knockdown of both ARFL and AR-Vs more potently suppressed cell growth, AR transcriptional activity, and AR-regulated gene expression than knockdown of ARFL alone. Exon-1 AR-ASO also inhibited tumor growth of LTL-313BR patient-derived CRPC xenografts.</jats:p>\n                  <jats:p>Conclusions: These data identify the AR as an important driver of ENZ resistance, and while the contributions of ARFL and AR-Vs can vary across cell systems, ARFL is the key driver in the ENZ-R LNCaP model. AR targeting strategies against both ARFL and AR-Vs is a rational approach for AR-dependent CRPC. Clin Cancer Res; 21(7); 1675–87. ©2015 AACR.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1030003658736006144","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"30593298"},{"@type":"NRID","@value":"1000030593298"},{"@type":"NRID","@value":"9000017343198"},{"@type":"NRID","@value":"9000413926984"},{"@type":"NRID","@value":"9000413498290"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/7000022350"}],"foaf:name":[{"@value":"Yoshiaki Yamamoto"}],"jpcoar:affiliationName":[{"@value":"1The Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada."},{"@value":"2Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, Japan."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995389521159","@type":"Researcher","foaf:name":[{"@value":"Yohann Loriot"}],"jpcoar:affiliationName":[{"@value":"1The Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995389521155","@type":"Researcher","foaf:name":[{"@value":"Eliana Beraldi"}],"jpcoar:affiliationName":[{"@value":"1The Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995389521167","@type":"Researcher","foaf:name":[{"@value":"Fan Zhang"}],"jpcoar:affiliationName":[{"@value":"1The Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995389521156","@type":"Researcher","foaf:name":[{"@value":"Alexander W. Wyatt"}],"jpcoar:affiliationName":[{"@value":"1The Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995389521157","@type":"Researcher","foaf:name":[{"@value":"Nader Al Nakouzi"}],"jpcoar:affiliationName":[{"@value":"1The Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995389521152","@type":"Researcher","foaf:name":[{"@value":"Fan Mo"}],"jpcoar:affiliationName":[{"@value":"1The Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995389521164","@type":"Researcher","foaf:name":[{"@value":"Tianyuan Zhou"}],"jpcoar:affiliationName":[{"@value":"3Department of Antisense Drug Discovery, Isis Pharmaceuticals Inc., Carlsbad, California."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995389521154","@type":"Researcher","foaf:name":[{"@value":"Youngsoo Kim"}],"jpcoar:affiliationName":[{"@value":"3Department of Antisense Drug Discovery, Isis Pharmaceuticals Inc., Carlsbad, California."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995389521165","@type":"Researcher","foaf:name":[{"@value":"Brett P. Monia"}],"jpcoar:affiliationName":[{"@value":"3Department of Antisense Drug Discovery, Isis Pharmaceuticals Inc., Carlsbad, California."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995389521166","@type":"Researcher","foaf:name":[{"@value":"A. Robert MacLeod"}],"jpcoar:affiliationName":[{"@value":"3Department of Antisense Drug Discovery, Isis Pharmaceuticals Inc., Carlsbad, California."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995389521161","@type":"Researcher","foaf:name":[{"@value":"Ladan Fazli"}],"jpcoar:affiliationName":[{"@value":"1The Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995389521153","@type":"Researcher","foaf:name":[{"@value":"Yuzhuo Wang"}],"jpcoar:affiliationName":[{"@value":"1The Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995389521158","@type":"Researcher","foaf:name":[{"@value":"Colin C. Collins"}],"jpcoar:affiliationName":[{"@value":"1The Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995389521162","@type":"Researcher","foaf:name":[{"@value":"Amina Zoubeidi"}],"jpcoar:affiliationName":[{"@value":"1The Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995389521160","@type":"Researcher","foaf:name":[{"@value":"Martin Gleave"}],"jpcoar:affiliationName":[{"@value":"1The Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada."}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"10780432"},{"@type":"EISSN","@value":"15573265"}],"prism:publicationName":[{"@value":"Clinical Cancer Research"}],"dc:publisher":[{"@value":"American Association for Cancer Research (AACR)"}],"prism:publicationDate":"2015-03-31","prism:volume":"21","prism:number":"7","prism:startingPage":"1675","prism:endingPage":"1687"},"reviewed":"false","url":[{"@id":"https://aacrjournals.org/clincancerres/article-pdf/21/7/1675/2030047/1675.pdf"}],"createdAt":"2015-01-30","modifiedAt":"2025-05-17","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Male","dc:title":"Male"},{"@id":"https://cir.nii.ac.jp/all?q=Reverse%20Transcriptase%20Polymerase%20Chain%20Reaction","dc:title":"Reverse Transcriptase Polymerase Chain Reaction"},{"@id":"https://cir.nii.ac.jp/all?q=Blotting,%20Western","dc:title":"Blotting, Western"},{"@id":"https://cir.nii.ac.jp/all?q=Antineoplastic%20Agents","dc:title":"Antineoplastic Agents"},{"@id":"https://cir.nii.ac.jp/all?q=Oligonucleotides,%20Antisense","dc:title":"Oligonucleotides, Antisense"},{"@id":"https://cir.nii.ac.jp/all?q=Transfection","dc:title":"Transfection"},{"@id":"https://cir.nii.ac.jp/all?q=Immunohistochemistry","dc:title":"Immunohistochemistry"},{"@id":"https://cir.nii.ac.jp/all?q=Xenograft%20Model%20Antitumor%20Assays","dc:title":"Xenograft Model Antitumor Assays"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Prostatic%20Neoplasms,%20Castration-Resistant","dc:title":"Prostatic Neoplasms, Castration-Resistant"},{"@id":"https://cir.nii.ac.jp/all?q=Drug%20Resistance,%20Neoplasm","dc:title":"Drug Resistance, Neoplasm"},{"@id":"https://cir.nii.ac.jp/all?q=Receptors,%20Androgen","dc:title":"Receptors, Androgen"},{"@id":"https://cir.nii.ac.jp/all?q=Benzamides","dc:title":"Benzamides"},{"@id":"https://cir.nii.ac.jp/all?q=Nitriles","dc:title":"Nitriles"},{"@id":"https://cir.nii.ac.jp/all?q=Phenylthiohydantoin","dc:title":"Phenylthiohydantoin"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Protein%20Isoforms","dc:title":"Protein Isoforms"},{"@id":"https://cir.nii.ac.jp/all?q=RNA,%20Small%20Interfering","dc:title":"RNA, Small Interfering"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004235490298752","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Collateral resistance to taxanes in enzalutamide‐resistant prostate cancer through aberrant androgen receptor and its 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