Imaging NFkB Activation in HTLV Lymphoma

这个项目将利用生物发光成像(BLI)来提供对分子的独特见解 炎症相关癌症的发病机制，与人类T细胞白血病病毒癌蛋白有关。税金。在……里面 这些研究我们将使用两种不同的动物模型。首先，我们将分析Tax转基因小鼠 不同的税收或NFkB BLI记者。其次，我们将分析一个移植模型，在该模型中，税收 携带甲虫绿色报告基因的转基因细胞系被移植到携带NFkB萤火虫的小鼠身上 荧光素酶BLI记者。我们将回答以下问题： 1)炎症是否通过激活NFkB途径促进淋巴瘤的发生？为此，IKB- LUC小鼠将用于监测带有或不带有T细胞的转基因或移植小鼠的NFkB活性 刀豆蛋白A激活(ConA)。Rel-A和Rel-A的BLI和IHC之间将进行关联。 B NFkB亚基。 2)在淋巴瘤的恶性和/或非恶性细胞中，哪个NFkB途径最重要 发展？为此，IKK1或IKK2删除了缺乏替代或经典NFkB的小鼠 途径将分别用于BLI和IHC研究的转基因和移植模型。 3)NFkB靶基因IL15在恶性和/或非恶性淋巴瘤的发生发展中起什么作用 恶性细胞？为此，我们将LL15缺失或IL15野生型税务淋巴瘤细胞移植到 IL15缺失或LL15野生型动物以确定每个细胞中这一关键的白细胞介素nale 车厢。 相关性(请参阅说明)： 总之，这些研究将利用BLI提供更精细的分子描述 NFkB在淋巴瘤中的激活与微环境

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.