Imaging NFkB Activation in HTLV Lymphoma

该项目将利用生物发光成像（BLI）提供独特的见解的分子 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。税在 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， 不同的税务或NFkB BLI记者。其次，我们将分析一个移植模型，其中一个税收 将携带点击甲虫绿色报道基因的转基因细胞系移植到携带NFkB萤火虫的小鼠上 荧光素酶BLI报告基因。我们将回答以下问题： 1)炎症是否通过激活NFkB通路促进淋巴瘤的发生？为此目的，IkB- Luc小鼠将用于监测具有或不具有T细胞的转基因或移植小鼠中的NFkB活化。 用伴刀豆球蛋白A（conA）激活。将在Rel-A和Rel-B的BLI和IHC之间进行相关性分析。 B NF κ B亚基。 2)哪种NFkB通路在淋巴瘤的恶性和/或非恶性细胞中最重要 发展？为此目的，选择性或经典NFkB缺陷的IKK 1或IKK 2缺失小鼠 将分别在BLI和IHC研究的转基因和移植模型中使用这些途径。 3)NFkB靶基因IL 15在恶性和/或非恶性淋巴瘤中的作用是什么？ 恶性细胞？为此目的，我们将IL 15缺失或IL 15野生型Tax淋巴瘤细胞移植到 在IL 15缺失或IL 15野生型动物中测定该关键白细胞介素的浓度，以确定每个细胞中该关键白细胞介素的浓度。 车厢 相关性（参见说明）： 总之，这些研究将利用BLI提供更精确的分子描述的作用， 淋巴瘤和微环境中的NFkB活化。

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.