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PAX2 is an antiapoptotic molecule with deregulated expression in medulloblastoma


Burger, M C; Brucker, D P; Baumgarten, P; Ronellenfitsch, M W; Wanka, C; Hasselblatt, M; Eccles, M R; Klingebiel, T; Weller, M; Rieger, J; Mittelbronn, M; Steinbach, J P (2012). PAX2 is an antiapoptotic molecule with deregulated expression in medulloblastoma. International Journal of Oncology, 41(1):235-241.

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.

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.

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3 citations in Web of Science®
3 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2012
Deposited On:08 Oct 2012 12:21
Last Modified:05 Apr 2016 15:57
Publisher:Spandidos
ISSN:1019-6439
Publisher DOI:10.3892/ijo.2012.1446
PubMed ID:22552444
Permanent URL: http://doi.org/10.5167/uzh-64655

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