{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:05:37Z","timestamp":1791389137830,"version":"4.3.3"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Revealing molecular mechanisms linked to androgen receptor activity can help to improve diagnosis and treatment of prostate cancer. Retinoic acid-induced 2 (RAI2) protein is thought to act as a transcriptional coregulator involved in hormonal responses and epithelial differentiation. We evaluated the clinical relevance and biological function of the RAI2 protein in prostate cancer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We assessed RAI2 gene expression in the Cancer Genome Atlas prostate adenocarcinoma PanCancer cohort and protein expression in primary tumors (n\u2009=\u2009199) by immunohistochemistry. We studied RAI2 gene expression as part of a multimarker panel in an enriched circulating tumor cell population isolated from blood samples (n\u2009=\u200938) of patients with metastatic prostate cancer. In prostate cancer cell lines, we analyzed the consequences of androgen receptor inhibition on RAI2 protein expression and the consequences of RAI2 depletion on the expression of the androgen receptor and selected target genes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Abundance of the RAI2 protein in adenocarcinomas correlated with the androgen receptor; keratins 8, 18, and 19; and E-cadherin as well as with an early biochemical recurrence. In circulating tumor cells, detection of RAI2 mRNA significantly correlated with gene expression of FOLH1, KLK3, RAI2, AR, and AR-V7. In VCaP and LNCaP cell lines, sustained inhibition of hormone receptor activity induced the RAI2 protein, whereas RAI2 depletion augmented the expression of MME, STEAP4, and WIPI1.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The RAI2 protein functions as a transcriptional coregulator of the androgen response in prostate cancer cells. Detection of RAI2 gene expression in blood samples from patients with metastatic prostate cancer indicated the presence of circulating tumor cells.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/clinchem\/hvac073","type":"journal-article","created":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T19:10:05Z","timestamp":1650913805000},"page":"973-983","source":"Crossref","is-referenced-by-count":6,"title":["Expression Patterns and Corepressor Function of Retinoic Acid-induced 2 in Prostate Cancer"],"prefix":"10.1093","volume":"68","author":[{"given":"Katharina","family":"Besler","sequence":"first","affiliation":[{"name":"Department of Tumor Biology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"W\u0119glarz","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunhild","family":"von Amsberg","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9506-942X","authenticated-orcid":false,"given":"Natalia","family":"Bednarz-Knoll","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany"},{"name":"Laboratory of Translational Oncology, Medical University of Gda\u0144sk , Gda\u0144sk , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Offermann","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Schleswig-Holstein, Campus L\u00fcbeck , L\u00fcbeck , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Stoupiec","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Eltze","sequence":"additional","affiliation":[{"name":"Institute of Pathology Saarbruecken-Rastpfuhl , Saarbruecken , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Semjonow","sequence":"additional","affiliation":[{"name":"Department of Urology, Prostate Center University Clinic M\u00fcnster , M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Boettcher","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Schneegans","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Perner","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Schleswig-Holstein, Campus L\u00fcbeck , L\u00fcbeck , Germany"},{"name":"Pathology, Research Center Borstel, Leibniz Lung Center , Borstel , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegfried","family":"Hauch","sequence":"additional","affiliation":[{"name":"QIAGEN Gmbh , Hilden , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman","family":"Todenh\u00f6fer","sequence":"additional","affiliation":[{"name":"Medical School, University of T\u00fcbingen , T\u00fcbingen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Peine","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine, University Medical Center Hamburg-Eppendorf , Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Pantel","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet","family":"Wikman","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2451-9371","authenticated-orcid":false,"given":"Stefan","family":"Werner","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany"},{"name":"Mildred-Scheel-Nachwuchszentrum HaTRiCs4, Universit\u00e4res Cancer Center Hamburg , Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"2022070317165976400_hvac073-B1","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.eururo.2016.05.043","article-title":"Global incidence and mortality for prostate cancer: analysis of temporal patterns and trends in 36 countries","volume":"70","author":"Wong","year":"2016","journal-title":"Eur 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Involvement of Wnt pathway activation","volume":"64","author":"Gattelli","year":"2004","journal-title":"Cancer Res"},{"key":"2022070317165976400_hvac073-B7","doi-asserted-by":"crossref","first-page":"11409","DOI":"10.1128\/JVI.00234-06","article-title":"Selection of early-occurring mutations dictates hormone-independent progression in mouse mammary tumor lines","volume":"80","author":"Gattelli","year":"2006","journal-title":"J Virol"},{"key":"2022070317165976400_hvac073-B8","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1210\/er.2002-0032","article-title":"Androgen receptor in prostate cancer","volume":"25","author":"Heinlein","year":"2004","journal-title":"Endocr Rev"},{"key":"2022070317165976400_hvac073-B9","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics 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epithelial-like phenotype and good prognosis in prostate cancer","volume":"203","author":"Nastaly","year":"2019","journal-title":"Transl Res"},{"key":"2022070317165976400_hvac073-B13","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1002\/ijc.31905","article-title":"Somatic aberrations of BRCA1 gene are associated with ALDH1, EGFR, and tumor progression in prostate cancer","volume":"144","author":"Omari","year":"2019","journal-title":"Int J Cancer"},{"key":"2022070317165976400_hvac073-B14","doi-asserted-by":"crossref","first-page":"4934","DOI":"10.1038\/sj.onc.1208677","article-title":"Molecular cloning and characterization of STAMP2, an androgen-regulated six transmembrane protein that is overexpressed in prostate cancer","volume":"24","author":"Korkmaz","year":"2005","journal-title":"Oncogene"},{"key":"2022070317165976400_hvac073-B15","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1038\/sj.embor.7401046","article-title":"New androgen receptor genomic targets show 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progression","volume":"74","author":"Takayama","year":"2014","journal-title":"Cancer Res"},{"key":"2022070317165976400_hvac073-B19","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.stemcr.2016.03.007","article-title":"Basal progenitors contribute to repair of the prostate epithelium following induced luminal anoikis","volume":"6","author":"Toivanen","year":"2016","journal-title":"Stem Cell Reports"},{"key":"2022070317165976400_hvac073-B20","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1006\/dbio.1994.1056","article-title":"Isolation and developmental expression of retinoic-acid-induced genes","volume":"161","author":"Jonk","year":"1994","journal-title":"Dev Biol"},{"key":"2022070317165976400_hvac073-B21","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s10549-021-06176-w","article-title":"Low RAI2 expression is a marker of poor prognosis in breast cancer","volume":"187","author":"Nishikawa","year":"2021","journal-title":"Breast Cancer Res Treat"},{"key":"2022070317165976400_hvac073-B22","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1097\/PPO.0000000000000220","article-title":"Clinical validity of detecting circulating tumor cells by AdnaTest assay compared with direct detection of tumor mRNA in stabilized whole blood, as a biomarker predicting overall survival for metastatic castration-resistant prostate cancer patients","volume":"22","author":"Danila","year":"2016","journal-title":"Cancer J"},{"key":"2022070317165976400_hvac073-B23","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1158\/2159-8290.CD-15-1483","article-title":"Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy","volume":"6","author":"Alix-Panabieres","year":"2016","journal-title":"Cancer Discov"},{"key":"2022070317165976400_hvac073-B24","doi-asserted-by":"crossref","first-page":"37022","DOI":"10.1038\/srep37022","article-title":"The correlation between expression profiles measured in single cells and in traditional bulk samples","volume":"6","author":"Dzamba","year":"2016","journal-title":"Sci Rep"},{"key":"2022070317165976400_hvac073-B25","first-page":"3507","article-title":"Preliminary experience on the use of the Adnatest(R) system for detection of circulating tumor cells in prostate cancer patients","volume":"32","author":"Todenhofer","year":"2012","journal-title":"Anticancer Res"},{"key":"2022070317165976400_hvac073-B26","first-page":"80","article-title":"The pathophysiologic basis of anaemia in patients with malignant diseases","volume":"1","author":"Ibrahim","year":"2016","journal-title":"Gulf J Oncolog"},{"key":"2022070317165976400_hvac073-B27","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/s41585-018-0060-7","article-title":"Landmarks in prostate cancer","volume":"15","author":"Sathianathen","year":"2018","journal-title":"Nat Rev Urol"},{"key":"2022070317165976400_hvac073-B28","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1006\/geno.1998.5667","article-title":"Identification and characterization of the human homologue (RAI2) of a mouse retinoic acid-induced gene in Xp22","volume":"55","author":"Walpole","year":"1999","journal-title":"Genomics"}],"container-title":["Clinical 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