title: PAX2 is an antiapoptotic molecule with deregulated expression in medulloblastoma.
abstract: PAX2 is a paired box transcription factor possessing a fundamental role             in the embryogenesis of hindbrain and urinary tract. PAX genes are proto-oncogenes,             PAX2 expression may contribute to the pathogenesis of renal cell carcinoma. Because             of the expression of PAX2 in the developing hindbrain and its essential role in             cerebellar development, it has been hypothesized that PAX2 may also be involved             in medulloblastoma tumorigenesis. We investigated the expression pattern of PAX2             and various genes of the neuronal lineage in medulloblastoma and glioma cell lines.             We found high expression of PAX2 mRNA and PAX2 protein in medulloblastoma cells             and some glioma cell lines independent of their neuronal lineage gene expression             signature. Gene suppression of PAX2 decreased the expression of the PAX2 transcriptional             target GDNF in Daoy cells and had a profound cytotoxic effect in vitro on Daoy             medulloblastoma and T98G glioma cells. Expression of PAX2 was then assessed in             two separate medulloblastoma tissue microarrays with a total of 61 patient samples             by immunohistochemistry. PAX2 expression was detected in the majority of medulloblastoma             samples and correlated with less differentiated histology. Therefore, PAX2 is             a biomarker for a more aggressive medulloblastoma phenotype and may represent             a novel therapeutic target.
authors.affiliation: Dr Senckenberg Institute of Neurooncology, Goethe-University Hospital Frankfurt, Frankfurt, Germany. michael.burger@kgu.de
authors.forename: M C
authors.initials: MC
authors.lastname: Burger
authors.forename: D P
authors.initials: DP
authors.lastname: Brucker
authors.forename: P
authors.initials: P
authors.lastname: Baumgarten
authors.forename: M W
authors.initials: MW
authors.lastname: Ronellenfitsch
authors.forename: C
authors.initials: C
authors.lastname: Wanka
authors.forename: M
authors.initials: M
authors.lastname: Hasselblatt
authors.forename: M R
authors.initials: MR
authors.lastname: Eccles
authors.forename: T
authors.initials: T
authors.lastname: Klingebiel
authors.forename: M
authors.initials: M
authors.lastname: Weller
authors.forename: J
authors.initials: J
authors.lastname: Rieger
authors.forename: M
authors.initials: M
authors.lastname: Mittelbronn
authors.forename: J P
authors.initials: JP
authors.lastname: Steinbach
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D051762:PAX2 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D051757:PAX5 Transcription Factor / Q000378:metabolism; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D034622:RNA Interference; D046888:Tissue Array Analysis
chemical_list: D000943:Antigens, Differentiation; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018398:Homeodomain Proteins; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors