SEARCH:   Advanced

Blood, 12 February 2009, Vol. 113, No. 7, pp. 1493-1500. Prepublished online as a Blood First Edition Paper on October 29, 2008; DOI 10.1182/blood-2008-07-166462. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-07-166462v1 113/7/1493    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rauch, D. Articles by Ratner, L. Search for Related Content PubMed PubMed Citation Articles by Rauch, D. Articles by Ratner, L. Related Collections Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Imaging spontaneous tumorigenesis: inflammation precedes development of peripheral NK tumors Dan Rauch1, Shimon Gross2, John Harding1, Stefan Niewiesk3, Michael Lairmore3,4, David Piwnica-Worms2,5, and Lee Ratner1 1 Department of Medicine, Division of Molecular Oncology and 2 Molecular Imaging Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO; 3 College of Veterinary Medicine and 4 Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus; and 5 Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO Early events in tumor development are spontaneous, microscopic, and affected by the microenvironment. We developed a mouse model of spontaneous lymphoma in which malignant transformation is coupled with light emission that can be detected noninvasively using bioluminescent imaging. The human T-cell leukemia virus (HTLV) type 1 transcriptional transactivator Tax is an oncogene sufficient to produce lymphoma in transgenic animal models. Using the granzyme B promoter to restrict Tax expression to the mature natural killer (NK)/T-cell compartment, we have reproduced many elements of HTLV-associated adult T-cell leukemia/lymphoma. Tax activates signaling cascades associated with transformation, inflammation, and tumorigenesis. Here, we report that Tax-mediated activation of luciferase in long terminal repeat-luciferase (LTR-LUC) mice serves as a reporter for imaging these processes in vivo. Using bioluminescent imaging (BLI), we discovered that microscopic intraepithelial lesions precede the onset of peripheral subcutaneous tumors, tumorigenesis progresses through early reversible stages, and Tax is sufficient for inducing tumors. Based on these findings, we propose that Tax expression in activated lymphocytes initiates a cascade of events that leads to NK/T cell recruitment, activation, and transformation. The use of BLI expands our ability to interrogate the role of Tax in tumorigenesis in vivo and has made the association of inflammation with tumor initiation amenable for study. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020