REGULATION OF TRANSGENE EXPRESSION

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Genetically initiated Tg.AC transgenic mice carry a transgene consisting of an oncogenic v-Ha-ras coding region flanked 5 by a mouse zetaglobin promoter and 3 by an SV-40 polyadenylation sequence. Located proximal to the centromere on chromosome 11, the transgene is transcriptionally silent until activated by full thickness wounding, UV light, or chemical carcinogens. This discriminating tumorigenic response does not occur when Tg.AC mice are treated with structurally similar non-carcinogenic chemicals. Expression of the transgene is a required early event that drives cellular proliferation resulting in clonal expansion and tumor formation. Genetic and epigenetic mechanism may contribute to this induced response. A very unique and specific assemblage of cis regions and transcription factors intrinsic to the tumorigenic process are required to activate the transgene following treatments with carcinogens. Our laboratory is interested in elucidating the induced tumorigenic response in Tg.AC v-Ha-ras transgenic mice. Our approach is to utilize molecular, genetic and biochemical techniques to identify the transcriptional control regions and the associated factors.