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000126670 0247_ $$2doi$$a10.1111/nan.12186
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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$$c2015
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000126670 520__ $$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.
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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
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