Malignant Rhabdoid Tumors (MRTs) show a loss of SNF5, a core subunit of the SWI/SNF chromatin remodeling complex. These cancers are genetically stable, but epigenetically unstable. We hypothesize that SNF5 loss fuels MRT development through aberrant gene expression by disruption of SWI/SNF remodeling. Introduction of SNF5 into MRTs activates the Rb-E2F pathway, resulting in G1 arrest. However, this pathway cannot completely account for the arrest. We identified two novel SNF5 targets that may contribute to arrest by PCR Array, Cyclin G2 and HERC5. Both show an increase in mRNA expression and SNF5 binding to their promoters by ChIP. Use of 4x44k expression arrays revealed that GDF15 might be a third novel target. Expression increases by mRNA and protein, but ChIP is needed for validation. These genes may be regulated by SNF5 and contribute to arrest after chromatin remodeling increases expression, possibly providing further insight into MRT development.
|Advisor:||Weissman, Bernard E.|
|Commitee:||Davis, Ian, Ramsden, Dale|
|School:||The University of North Carolina at Chapel Hill|
|School Location:||United States -- North Carolina|
|Source:||MAI 50/02M, Masters Abstracts International|
|Subjects:||Toxicology, Surgery, Oncology|
|Keywords:||Cyclin G2, Growth Differentiation Factor 15, Switch/Sucrose Non-Fermenting|
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