M edulloblastoma is an invasive embryonic tumor of the cerebellum with predominant neuronal differentiation. It is the most common malignant brain tumor of childhood, which mainly occurs between 5 and 10 years of age.(1) Despite recent advances in understanding the pathogenesis of medulloblastoma, the specific genetic alterations and molecular mechanisms involved in the brain tumor are not well defined.(2) It is generally accepted that medulloblastoma, like other cancers, represents a genetic disease of somatic cell alterations, such as gene mutations, deletions, translocations, or amplifications. The etiology and risk factors that contribute to the genetic aberrations for the tumors remain to be elucidated. It has been reported that aberrant activations of several cell signal pathways, such as Shh (3,4) Wnt (5,6) ErbB2 (7,8) and insulin-like growth factor 1-R (IGF1-R) pathways (9,10) were implicated in the pathological processes of brain tumors.Simian virus 40 (SV40) has been detected in medulloblastoma. (11,12) Several lines of evidence indicated that the viral early protein T antigen could be involved in the tumorigenesis process. SV40 T antigen (SV40Tag) is a multifunctional regulatory protein that binds to the tumor suppressor genes, including p53 (13) and the retinoblastoma (Rb) family of proteins.Furthermore, the antigen could interact with insulin receptor substrate I (IRS-1), which plays a critical role in transforming R-cells. (15,16) It is known that the interactions between SV40 Tantigen (SV40Tag) and tumor suppressor proteins stimulate DNA duplication, facilitate cell proliferation and induce cell transformation. (17,18) However, the molecular mechanism of the SV40 induction of tumors is not completely clear.Transgenic technology has provided a way to determine whether a particular gene product could contribute to the neoplastic process.Furthermore, the transgenic animal models could be used for studies on tumor development, progression and therapeutic targets identification and evaluation. Recently, a number of SV40Tag transgenic animal models have been reported, in which the transgene was constitutively expressed. (19)(20)(21)(22)(23)(24) These animal models were used for the studies of neoplastic development, as well as the equilibrium between proliferation and cell death. (25)(26)(27) However, the constitutive expression of SV40Tag may affect the development of the animal and therefore, hamper the analysis of critical steps of tumorigenesis. In an attempt to circumvent these limitations, we generated inducible transgenic mice expressing SV40Tag under the control of tetracycline. In this report, we have described the generation and molecular characterization of the tetracyclineresponsive SV40Tag transgenic mouse model for medulloblastoma. Materials and MethodsGeneration of the inducible SV40Tag transgenic mice. A 2.5-kb fragment containing the SV40Tag gene from pBC-SV40Tag (28) was generated with Xho I digestion and cloned into the Sal I site of pTRE-2 DNA vector (pTRE-SV40Tag). Linearized pTRE-S...

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SV40Tag transgenic mouse model can be successfully established. The transgenic mice develop a pancreatic tumor, which can be used for investigation of the molecular mechanism of tumorigenesis in vivo.

AIM:T o s t u d y t h e g e n e e x p r e s s i o n c h a n g e s i n pancreatic cystic neoplasm in SV40Tag transgenic mice model and to provide information about the prevention, clinical diagnosis and therapy of pancreatic cancer. METHODS:Using the pBC-SV40Tag transgenic mice model of pancreatic cystic neoplasm, we studied the gene expression changes by applying high-density microarrays. Validation of part gene expression profiling data was performed using real-time PCR.RESULTS: By using high-density oligonucleotide microarray, of 14 113 genes, 453 were increased and 760 decreased in pancreatic cystic neoplasm, including oncogenes, cell-cycle-related genes, signal transductionrelated genes, skeleton-related genes and metabolismrelated genes. Among these, we confirmed the changes in Igf, Shh and Wnt signal pathways with real-time PCR. The results of real-time PCR showed similar expression changes in gene chip.CONCLUSION: all the altered expression genes are associated with cell cycle, DNA damage and repair, signal pathway, and metabolism. SV40Tag may cooperate with several proteins in promoting tumorigenesis.