Investigating the Role of ASC in Medulloblastoma (2013)
Undergraduates: Esita Patel, Beth Knight
Faculty Advisor: Mohanish Deshmukh
Department: Biology
Medulloblastoma is a malignant childhood cancer of the neuronal progenitor cells of the cerebellum. Better understanding the pathways that lead to this cancer may help new treatments to be developed. We are currently investigating the role of TMS1 (target of methylation-induced silencing) in a Smoothened transgenic (SmoA1) medulloblastoma mouse model. We observed that, on a SmoA1 background, TMS1-/- (knockout) mice have a reduction in tumorigenesis compared to the TMS1+/+ (wild-type) mice. To explore how TMS1 is causing this difference, we conducted a gene expression microarray on SmoA1 mice cerebella which compared TMS1-/- to TMS1+/+ samples. This microarray revealed that many genes in the TGF-β pathway were being differentially expressed with TMS1. Using real-time RT-PCR to further investigate the genes in this pathway, we observed that multiple genes in the TGF-β pathway including Tgfb1i1, CyclinD1, Tgif1, and CDK2 were significantly differentially expressed with TMS1. Additional genes in this pathway also showed a general trend of differential expression with TMS1. These findings suggest that TMS1 regulates the TGF-β pathway, providing a new target to consider when developing treatments for medulloblastoma.