Gene Expression Analysis Of Medulloblastoma In SV40Tag Transgenic Mice Model

Medulloblastoma, the most common brain tumor in children, is a kind of primitive neuroectodermal tumor (PNETs) of cerebellum and account for approximately 25% of all the tumors in CNS of childhood. It is a major cause of brain cancer mortality. Recently, some reports show that the changes of Sonic Hedgehog (Shh), Wnt, erbB-2 and Igf signaling pathways can be detected in the development of medulloblastoma.SV40 belongs to polyoma virus. The character of its tumorigenesis is mostly related to T antigen-early protein. Epidemiology shows that it's genomic DNA sequence can be detected in human tumor. But the mechanism of the tumorigenesis of SV40Tag is not clear. On the basis of pTet-on, pTRE2-SV40Tag transgenic mice model of brain tumor established in our lab successfully, we identified what kind of brain tumor in this model firstly. The result showed that this mice model was medulloblastoma. Next, we applied microarray to study the gene expression changes of this tumor. The expression changes of Igf and erbB-2 were distinct. To further confirm the gene expression profiling data from gene chip, we performed real-time PCR and western-blotting. The results showed that the expression changes in both gene chip and real-time PCR were similar.By immunohistochemistry and co-immunoprecipitation, we also found that SV40Tag could interact with IRS-1, a member of Igf signaling pathway, and result in translocation of IRS-1. This result suggests that SV40Tag may active Igf signaling pathway by interaction with IRS-1, and promote tumorigenesis.In a word, we analysed the gene expression of pTet-on, pTRE2-SV40Tag transgenicmice model. The results suggest that SV40Tag actives Igf and erbB-2 signaling pathway, and promotes tumorigenesis. This will provide some information for the prevention, clinical diagnose and cure of medulloblastoma.