CNSC-32. ACTIN SUBUNIT STRUCTURAL DIVERSITY IN SHH MEDULLOBLASTOMA: IMPLICATIONS FOR CANCER BIOLOGY AND NEURODEVELOPMENT

Abstract BACKGROUND Altered expression of actin subunits is found in multiple cancers. Alpha-cardiac (ACTC1) expressed sonic hedgehog medulloblastoma (SHH MB) and regulates both cell survival migration. We hypothesized that cardiac has a unique structural functional role SHH MB may be post-natal granule progenitors (GCPs) which share similar gene profiles. METHODS Actin subunit protein (ACTC1, ACTB, ACTG1, ACTA2) was evaluated by mRNA profiling within established datasets across lines Western blot (WB). Immunofluorescence microscopy performed to assess intracellular localization. The composition each filamentous (F-) evaluated. Furthermore immunoprecipitation ACTC1 protein-protein interactions. ratio F-actin globular (G-) determined WB cells exposed mitotic inhibitor. Cell viability colony formation following over-expression dominant-negative mutant (P116C & G247D). RESULTS ACTC1, ACTB are the predominant MB. demonstrated co-localization with ACTG1 but not ACTA2. showed cortical localization pattern. Post-natal MATH1 positive mouse GCPs (P3-5) demonstrate distribution F-actin. analysis pulldown from fractions co-precipitation G-actin maintained show resistance inhibition. Expression G247D resulted reduced survival. CONCLUSIONS incorporated into GCPs. Filamentous forms complex ACTB. Disruption polymerization results These findings suggest important cerebellar development.