Paired overexpression of ErbB3 and Sox10 in pilocytic astrocytoma.

Abstract:

:Pilocytic astrocytoma (PA) is the most common glioma of childhood. Despite their relatively high incidence, the molecular mechanisms responsible for tumorigenesis and growth of PA are poorly understood. Previous in vitro studies in our laboratory showed that despite the absence of ErbB1, PA was sensitive to ErbB1 tyrosine kinase inhibitor gefitinib. To identify alternative targets of gefitinib in PA, we studied other members of the ErbB receptor tyrosine kinase family that have been identified in brain tumors. Using gene expression microarray and Western blot analyses, we found that ErbB3 is highly overexpressed in PA compared with other pediatric brain tumors (glioblastoma, ependymoma, medulloblastoma, atypical teratoid/rhabdoid tumor, and choroid plexus papilloma). Developmental biology studies have identified Sox10 as a regulator of ErbB3 expression during development of the neural crest. Investigation of Sox10 in PA revealed that it is highly overexpressed relative to other pediatric brain tumors, lending support to the theory that Sox10-regulated overexpression of ErbB3 may be driving growth in PA. Sox10-regulated ErbB3 overexpression is a novel insight into the biology of PA, suggests possible recapitulation of developmental pathways in tumorigenesis, and presents possible targets for therapeutic intervention that might be used for hypothalamic variants not amenable to surgical cure.

authors

Addo-Yobo SO,Straessle J,Anwar A,Donson AM,Kleinschmidt-Demasters BK,Foreman NK

doi

10.1097/01.jnen.0000229989.25171.aa

subject

Has Abstract

pub_date

2006-08-01 00:00:00

pages

769-75

issue

8

eissn

0022-3069

issn

1554-6578

pii

00005072-200608000-00004

journal_volume

65

pub_type

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