Function of Brg1 Chromatin Remodeling Factor in Sonic Hedgehog-Dependent Medulloblastoma Initiation and Maintenance
Abstract
Medulloblastoma is the most common malignant pediatric brain tumor. Overactive Shh signaling in cerebellum granule neuron precursors (CGNPs) is the leading cause of the childhood medulloblastoma (Shh-subtype). Previously we showed that chromatin remodeler Brg1 deletion resulted in reduced proliferation of CGNPs in developing cerebellum due to impaired Shh-activated target gene expression. Current study focuses on the requirement of Brg1 in mouse model of Shh-subtype medulloblastoma. Evidences showed that Brg1 is required for SmoM2-dependent CGNP mitogenic target gene expression and proliferation in cultures. Through conditional knockout Brg1 in primary cultured medulloblastoma cells, tumor growth was inhibited. Induction of Brg1 deletion in subcutaneous transplantation led to tumor aggression significant blocked. qRT-PCR and Western Blot showed that Shh-dependent mitogic target genes are decreased by knockout of Brg1. Systematic analyses of how BAF complexes regulate tumor growth will be performed to uncover the mechanism of medulloblastoma development at chromatin level. These studies will provide insights for drug development and therapy of pediatric brain tumor and other Shh-dependent tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA599190
Entities
People
- Jiang Wu
- Xuanming Shi
Organizations
- University of Texas at Dallas