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Blood, 1 August 2004, Vol. 104, No. 3, pp. 802-809. Prepublished online as a Blood First Edition Paper on April 15, 2004; DOI 10.1182/blood-2003-11-3967. This Article Full Text (PDF) All Versions of this Article: 2003-11-3967v1 104/3/802    most recent Alert me when this article is cited Alert me if a correction is posted 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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mitra-Kaushik, S. Articles by Ratner, L. Search for Related Content PubMed PubMed Citation Articles by Mitra-Kaushik, S. Articles by Ratner, L. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 26, 2003 Accepted March 14, 2004 Effects of the Proteasome Inhibitor PS-341 on Tumor Growth in HTLV-1 Tax Transgenic Mice and Tax Tumor Transplants Shibani Mitra-Kaushik, John C Harding, Jay Hess, and Lee Ratner* Medicine, Washington University, St Louis, MO, USA Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA * Corresponding author; email: lratner{at}im.wustl.edu. Recent studies have shown that the transcription factor, nuclear factor B (NF-B), regulates critical survival pathways in a variety of cancers, including HTLV-1 transformed CD4 T cells. The activation of NF-B is controlled by proteasome-mediated degradation of the inhibitor of nuclear factor B (IB). We investigated the effects of PS-341, a peptide boronate inhibitor of the proteasome in HTLV-1 Tax transgenic tumors in vitro and in vivo. In Tax transgenic mice, PS-341 administered thrice weekly-inhibited tumor associated NF-B activity. Quantitation of proliferation, apoptosis, IL-6 and IL-10 secretion by tumor cells in culture revealed that the effects of PS-341 on cell growth largely correlated with inhibition of NF-B mediated pathways. However, the effect of PS-341 on the growth of tumors in Tax transgenic mice revealed heterogeneity in drug responsiveness. The PS-341 treated tumor tissues show no consistent inhibition of NFB activation in vivo. Annexin V staining indicated that PS-341 response in vivo correlated with sensitivity to -irradiation induced apoptosis. On the other hand, transplanted Tax tumors in Rag-1 mice showed consistent inhibition of tumor growth and prolonged survival in response to the same drug regimen. TUNEL staining indicated that PS-341 treatment sensitizes Tax tumors to DNA fragmentation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. A. Pise-Masison, M. Radonovich, K. Dohoney, J. C. Morris, D. O'Mahony, M.-J. Lee, J. Trepel, T. A. Waldmann, J. E. Janik, and J. N. Brady Gene expression profiling of ATL patients: compilation of disease-related genes and evidence for TCF4 involvement in BIRC5 gene expression and cell viability Blood, April 23, 2009; 113(17): 4016 - 4026. [Abstract] [Full Text] [PDF] D. Rauch, S. Gross, J. Harding, S. Niewiesk, M. Lairmore, D. Piwnica-Worms, and L. Ratner Imaging spontaneous tumorigenesis: inflammation precedes development of peripheral NK tumors Blood, February 12, 2009; 113(7): 1493 - 1500. [Abstract] [Full Text] [PDF] S. T. Shu, M. V.P. Nadella, W. P. Dirksen, S. A. Fernandez, N. K. Thudi, J. L. Werbeck, M. D. Lairmore, and T. J. Rosol A Novel Bioluminescent Mouse Model and Effective Therapy for Adult T-Cell Leukemia/Lymphoma Cancer Res., December 15, 2007; 67(24): 11859 - 11866. [Abstract] [Full Text] [PDF] P. Zou, J. Kawada, L. 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