000126670 001__ 126670 000126670 005__ 20240228140840.0 000126670 0247_ $$2doi$$a10.1111/nan.12186 000126670 0247_ $$2pmid$$apmid:25287489 000126670 0247_ $$2ISSN$$a0305-1846 000126670 0247_ $$2ISSN$$a1365-2990 000126670 0247_ $$2altmetric$$aaltmetric:2757205 000126670 037__ $$aDKFZ-2017-02698 000126670 041__ $$aeng 000126670 082__ $$a610 000126670 1001_ $$0P:(DE-He78)b15b56a6ed37417d476470c60c0140ff$$aHarter, Patrick$$b0$$eFirst author$$udkfz 000126670 245__ $$aPaired box gene 8 (PAX8) expression is associated with sonic hedgehog (SHH)/wingless int (WNT) subtypes, desmoplastic histology and patient survival in human medulloblastomas. 000126670 260__ $$aOxford [u.a.]$$bWiley-Blackwell$$c2015 000126670 3367_ $$2DRIVER$$aarticle 000126670 3367_ $$2DataCite$$aOutput Types/Journal article 000126670 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1530859837_29427 000126670 3367_ $$2BibTeX$$aARTICLE 000126670 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000126670 3367_ $$00$$2EndNote$$aJournal Article 000126670 520__ $$aThe paired box gene 8 (PAX8) plays crucial roles in organ patterning and cellular differentiation during development and tumorigenesis. Although its function is partly understood in vertebrate development, there is poor data concerning human central nervous system (CNS) development and brain tumours.We investigated developing human (n = 19) and mouse (n = 3) brains as well as medulloblastomas (MBs) (n = 113) for PAX8 expression by immunohistochemistry. Human MB cell lines were assessed for PAX8 expression using polymerase chain reaction and immunoblotting and analysed for growth and migration following PAX8 knock-down by small interfering ribonucleic acid (siRNA).PAX8 protein expression was associated with germinal layers in human and murine forebrain and hindbrain development. PAX8 expression significantly decreased over time in the external granule cell layer but increased in the internal granule cell layer. In MB subtypes, we observed an association of PAX8 expression with sonic hedgehog (SHH) and wingless int subtypes but not with group 3 and 4 MBs. Beyond that, we detected high PAX8 levels in desmoplastic MB subtypes. Univariate analyses revealed high PAX8 levels as a prognostic factor associated with a significantly better patient prognosis in human MB (overall survival: Log-Rank P = 0.0404, Wilcoxon P = 0.0280; progression-free survival: Log-Rank P = 0.0225; Wilcoxon P = 0.0136). In vitro assays revealed increased proliferation and migration of MB cell lines after PAX8 siRNA knock-down.In summary, high PAX8 expression is linked to better prognosis in MBs potentially by suppressing both proliferative and migratory properties of MB cells. The distinct spatio-temporal expression pattern of PAX8 during brain development might contribute to the understanding of distinct MB subtype histogenesis. 000126670 536__ $$0G:(DE-HGF)POF3-319H$$a319H - Addenda (POF3-319H)$$cPOF3-319H$$fPOF III$$x0 000126670 588__ $$aDataset connected to CrossRef, PubMed, 000126670 650_7 $$2NLM Chemicals$$aHedgehog Proteins 000126670 650_7 $$2NLM Chemicals$$aPAX8 Transcription Factor 000126670 650_7 $$2NLM Chemicals$$aPAX8 protein, human 000126670 650_7 $$2NLM Chemicals$$aPaired Box Transcription Factors 000126670 650_7 $$2NLM Chemicals$$aRNA, Small Interfering 000126670 650_7 $$2NLM Chemicals$$aSHH protein, human 000126670 650_7 $$2NLM Chemicals$$aWnt Proteins 000126670 7001_ $$aBaumgarten, Peter$$b1 000126670 7001_ $$aZinke, Jenny$$b2 000126670 7001_ $$aSchilling, Karl$$b3 000126670 7001_ $$aBaader, Stefan$$b4 000126670 7001_ $$aHartmetz, Ann-Kathrin$$b5 000126670 7001_ $$aSchittenhelm, Jens$$b6 000126670 7001_ $$aBeschorner, Rudi$$b7 000126670 7001_ $$0P:(DE-HGF)0$$aLiebner, Stefan$$b8 000126670 7001_ $$aSchulte, Dorothea$$b9 000126670 7001_ $$0P:(DE-HGF)0$$aPlate, Karl-Heinz$$b10 000126670 7001_ $$aGutwein, Paul$$b11 000126670 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b12$$udkfz 000126670 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b13$$udkfz 000126670 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b14$$udkfz 000126670 7001_ $$0P:(DE-HGF)0$$aDoberstein, Kai$$b15 000126670 7001_ $$0P:(DE-He78)3494efbbc54460b109fe9eab0595adda$$aMittelbronn, Michel$$b16$$eLast author$$udkfz 000126670 773__ $$0PERI:(DE-600)2008293-9$$a10.1111/nan.12186$$gVol. 41, no. 2, p. 165 - 179$$n2$$p165 - 179$$tNeuropathology & applied neurobiology$$v41$$x0305-1846$$y2015 000126670 909CO $$ooai:inrepo02.dkfz.de:126670$$pVDB 000126670 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)b15b56a6ed37417d476470c60c0140ff$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ 000126670 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b8$$kDKFZ 000126670 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b10$$kDKFZ 000126670 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aDeutsches Krebsforschungszentrum$$b12$$kDKFZ 000126670 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aDeutsches Krebsforschungszentrum$$b13$$kDKFZ 000126670 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)551bb92841f634070997aa168d818492$$aDeutsches Krebsforschungszentrum$$b14$$kDKFZ 000126670 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b15$$kDKFZ 000126670 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)3494efbbc54460b109fe9eab0595adda$$aDeutsches Krebsforschungszentrum$$b16$$kDKFZ 000126670 9131_ $$0G:(DE-HGF)POF3-319H$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vAddenda$$x0 000126670 9141_ $$y2015 000126670 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNEUROPATH APPL NEURO : 2015 000126670 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000126670 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000126670 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000126670 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search 000126670 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC 000126670 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List 000126670 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index 000126670 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000126670 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000126670 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences 000126670 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews 000126670 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5 000126670 9201_ $$0I:(DE-He78)L101-20160331$$kL101$$lDKTK Heidelberg$$x0 000126670 9201_ $$0I:(DE-He78)L501-20160331$$kL501$$lDKTK Frankfurt$$x1 000126670 9201_ $$0I:(DE-He78)B062-20160331$$kB062$$lPädiatrische Neuroonkologie$$x2 000126670 9201_ $$0I:(DE-He78)G380-20160331$$kG380$$lKKE Neuropathologie$$x3 000126670 980__ $$ajournal 000126670 980__ $$aVDB 000126670 980__ $$aI:(DE-He78)L101-20160331 000126670 980__ $$aI:(DE-He78)L501-20160331 000126670 980__ $$aI:(DE-He78)B062-20160331 000126670 980__ $$aI:(DE-He78)G380-20160331 000126670 980__ $$aUNRESTRICTED