Characterization And Pathogenesis Analysis Of Islet Cell Tumor In SV40Tag Transgenic Rat Model

Simian virus 40 T antigen (SV40Tag) is a virus oncogene encoded by simian virus 40 (SV40). SV40Tag protein is a multifunctional regulatory protein that binds to and inactivates tumor suppressor genes, including p53 and pRb. It has been shown that interation between SV40Tag and suppressor proteins simulates DNA duplication, thus facilitating cell proliferation and inducing cell transformation. A number of SV40Tag transgenic animal tumor models have been established, including pancreatic cancer, bone sarcoma, urinary bladder carcinoma and liver cancer. But there is few animal models of pancreatic islets cell tumors. It is the one of the Neuroendocrine neoplasms, mainly arise from the insulin cells. The disease was difficultly diagnosised because of no specificity except glycopenia. The mechanism of the disease isn't clear and relatively investigation was little up to now. The aim of this work would establish a islet cell turmor model by SV40Tag transgenic rat.In our study, we microinjected into the male pronucleus of fertilized zygotes of SD rat with pBC-SV40Tag, obtained SV40Tag positive rat. By PCR, RT-PCR and Western Blotting analysis, it has been investigated that SV40Tag was only expressed in pancreas of the transgenic rat. Pancreatic tumors were appeared in about 80% positive rats.Then we charaterized the tumor by immunohistochemology and glucose test. Results demonstrated that the SV40Tag transgenic rat develop a pancreatic islet tumor. Based on the real-time PCR and Western Blotting analysis, we founded that IRS-1 was translocated from cytoplasm into nuclear, and appeared high expression at the presence of SV40Tag. IRS-1 was a importment protein in the signal pathway of IGF-IR .These results strongly suggested that SV40Tag may activate IGF signaling pathway for promoting tumorigenesis.In summary, SV40Tag transgenic rat was developed and the neoplasms induced by SV40Tag had been characterized as the pancreatic islet tumor. The transgenic animal model might lay basic foundation to the mechanism research, clinic diagnosis, prevention and thearphy of pancreatic islet tumor and SV40Tag tumorigenesis.