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.

Public Health Relevance

Altogether, these studies will exploit BLI to provide a more refined molecular description ofthe role of NFkB activation in lymphomas and the microenvironment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
2P50CA094056-12
Application #
8195497
Study Section
Special Emphasis Panel (ZCA1-SRLB-9 (M1))
Project Start
2012-01-01
Project End
2016-12-31
Budget Start
2012-08-27
Budget End
2012-12-31
Support Year
12
Fiscal Year
2012
Total Cost
$116,457
Indirect Cost
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Powell, Emily; Shao, Jiansu; Yuan, Yuan et al. (2016) p53 deficiency linked to B cell translocation gene 2 (BTG2) loss enhances metastatic potential by promoting tumor growth in primary and metastatic sites in patient-derived xenograft (PDX) models of triple-negative breast cancer. Breast Cancer Res 18:13
Al-Hussaini, Muneera; Rettig, Michael P; Ritchey, Julie K et al. (2016) Targeting CD123 in acute myeloid leukemia using a T-cell-directed dual-affinity retargeting platform. Blood 127:122-31
Miller, Jessica P; Egbulefu, Christopher; Prior, Julie L et al. (2016) Gradient-Based Algorithm for Determining Tumor Volumes in Small Animals Using Planar Fluorescence Imaging Platform. Tomography 2:17-25
Ruhland, Megan K; Loza, Andrew J; Capietto, Aude-Helene et al. (2016) Stromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis. Nat Commun 7:11762
Thomas, Jane J; Abed, Mona; Heuberger, Julian et al. (2016) RNF4-Dependent Oncogene Activation by Protein Stabilization. Cell Rep 16:3388-400
Som, Avik; Raliya, Ramesh; Tian, Limei et al. (2016) Monodispersed calcium carbonate nanoparticles modulate local pH and inhibit tumor growth in vivo. Nanoscale 8:12639-47
Perera, Sandun; Piwnica-Worms, David; Alauddin, Mian M (2016) Synthesis of a [(18)F]-labeled ceritinib analogue for positron emission tomography of anaplastic lymphoma kinase, a receptor tyrosine kinase, in lung cancer. J Labelled Comp Radiopharm 59:103-8
Luo, Xianmin; Fu, Yujie; Loza, Andrew J et al. (2016) Stromal-Initiated Changes in the Bone Promote Metastatic Niche Development. Cell Rep 14:82-92
Chen, Yi-Hsien; Cimino, Patrick J; Luo, Jingqin et al. (2016) ABCG1 maintains high-grade glioma survival in vitro and in vivo. Oncotarget 7:23416-24
Sun, Jessica; Miller, Jessica P; Hathi, Deep et al. (2016) Enhancing in vivo tumor boundary delineation with structured illumination fluorescence molecular imaging and spatial gradient mapping. J Biomed Opt 21:80502

Showing the most recent 10 out of 251 publications