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Make Money. Find a job. Get paid.. Enter a demand-expected time series or a simple ratio of demands-to-supplies. Free Invader Zim 3D Invader Zim Dreams Invader.The long-term objective of this proposal is to investigate the molecular events that regulate the expression and function of a set of genes important for medulloblastoma and metastasis, including members of the human K-ras oncogene family. To accomplish this objective, we have developed experimental paradigms that will enable us to assess the role of novel genetic, epigenetic, and environmental factors in the process of tumor formation in transgenic mice. Our laboratory has demonstrated the development of medulloblastoma in ras-2 mutant C3H mice infected at birth with ras-1 or ras-2, two members of the ras gene family. This work has been expanded in a recent proposal to develop a mouse model of ras-2-driven medulloblastoma. Recently, we have shown that C3H mice infected with ras-1, but not ras-2, genes express the v-Ki-ras transgene. In these mice, brain tumors have been found to express all members of the human K-ras gene family with the exception of the human Ki-ras-1 gene. Therefore, the presence of this oncogene appears to result in an inability to transactivate its normal cellular counterpart and restrict it to the neuronal compartment. In collaboration with other groups, we have used micro-chromosome inversions to rescue the oncogenes in those tumors that express ras genes from their normal chromosomal arrangement. In mouse embryo fibroblasts that are deficient for myc or c-ras, the protein kinase C inhibitor known as bis-indolylmaleimide (BIM-I) inhibits the growth of the transformed cells but not the nontransformed cells. In this proposal, we plan to investigate further the role of PKC in mediating ras gene expression in human and mouse cells. We have shown that ras gene expression is controlled, in part, at the level of transcription of the ras gene via a cis-acting element known as the ras response element (RRE). We have recently
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