Coexpression of neuronatin splice forms promotes medulloblastoma growth.

Abstract:

:Medulloblastoma (MB) is the most common pediatric brain cancer. Several important developmental pathways have been implicated in MB formation, but fewer therapeutic targets have been identified. To locate frequently overexpressed genes, we performed a comprehensive gene expression survey of MB. Our comparison of 20 primary tumors to normal cerebellum identified neuronatin (NNAT) as the most frequently overexpressed gene in our analysis. NNAT is a neural-specific developmental gene with alpha and beta splice forms. Functional evaluation revealed that RNA interference knockdown of NNAT causes a significant decrease in proliferation. Conversely, coexpression of both splice forms in NNAT-negative MB cell lines increased proliferation, caused a significant shift from G(1) to G(2)/M, and increased soft agar colony formation and size. When expressed individually, each NNAT splice form had much less effect on these in vitro oncogenic predictors. In an in vivo model, the coexpression of both splice forms conferred the ability of xenograft formation to human MB cells that do not normally form xenografts, whereas a control gene had no effect. Our findings suggest that the frequently observed overexpression of both NNAT splice forms in MB enhances growth in this cancer.

journal_name

Neuro Oncol

journal_title

Neuro-oncology

authors

Siu IM,Bai R,Gallia GL,Edwards JB,Tyler BM,Eberhart CG,Riggins GJ

doi

10.1215/15228517-2008-038

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

716-24

issue

5

eissn

1522-8517

issn

1523-5866

pii

15228517-2008-038

journal_volume

10

pub_type

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