Imaging NFkB Activation in HTLV Lymphoma

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This project will utilize bioluminescence imaging (BLI) to provide unique insights into the molecular pathogenesis of inflammation-associated cancer, with the human T-cell leukemia virus oncoprotein. Tax. In these studies we will use two different animal models. First, we will analyze Tax transgenic mice with different Tax or NFkB BLI reporters. Second, we will analyze a transplantation model in which a Tax transgenic cell line carrying a click beetle green reporter is grafted onto mice carrying a NFkB firefly luciferase BLI reporter. We will answer the following questions: 1) Does inflammation promote lymphoma through activation ofthe NFkB pathway? Forthis purpose IkB- Luc mice will be used to monitor NFkB activation in transgenic or transplanted mice with or without T cell activation with concanavalin A (con A). Correlation will be perfonned between BLI and IHC of Rel-A and Rel- B NFkB subunits. 2) Which NFkB pathway is most important in the malignant and/or non-malignant cells for lymphoma development? Forthis purpose IKK1 or IKK2 deleted mice deficient in the alternative or classical NFkB pathways, respectively, will be used in the transgenic and transplantation models for BLI and IHC studies. 3) What is the role in lymphoma development of the NFkB-target gene, IL15, in malignant and/or non- malignant cells? Forthis purpose, we will transplant lL15-deleted or IL15-wild type Tax lymphoma cells into IL15-deleted or lL15-wild type animals to determine the nale of this critical interieukin in each cellular compartment. RELEVANCE (See instructions): Altogether, these studies will exploit BLI to provide a more refined molecular description ofthe role of NFkB activation in lymphomas and the microenvironment.