Identification And Pathogenesis Analysis Of Medulloblastoma In A Transgenic Mouse Model

SV40 belongs to polyomavirus and epidemiology shows that the genomic DNA sequence of SV40 can be detected in human brain tumor. 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. The character of tumorigenesis is most likely related to T antigen-early protein of SV40. But the mechanism of the tumorigenesis of SV40 is not clear.It has been reported that the change of Sonic Hedgehog (SHH), Wnt, Notch erbB-2 and IGF signaling pathways could be detected in the development of medulloblastoma. Recently, we have generated a pTRE2-SV40Tag agtransgenic mice model of brain tumor. Histological analysis showed that the brain tumor belonged to medulloblastoma. We applied DNA microarray and real-time PCR to study the gene expression changes in the brain tumor. Our results demonstrated that the expression levels of genes in IGF signaling pathway and erbB-2 were altered significantly.To study the molecular mechanism and signal pathways of the brain tumor, we have established the mouse Medulloblastoma cell line from the tumor tissue. We found that IRS-1 was translocated from the cytoplasm into nuclear at the presence of SV40Tag using immunohistochemistry and immunofluorescence methods. These results strongly suggested that SV40Tag may activate IGF signaling pathway for promoting tumorigenesis.In summary, we analyzed the gene expression and signal pathways of pTRE2-SV40Tag transgenic mice model. The results showed that SV40Tag activated IGF (?) signaling pathways, resulted in the translocation of IRS-1 into nuclear,and promotes tumorigenesis. These results provided important information fcr the understanding of the molecular mechanisms of the tumorigenesis in medulloblastoma.