This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yamochi, T. Articles by Dang, N. H. Search for Related Content PubMed PubMed Citation Articles by Yamochi, T. Articles by Dang, N. H.

Regulation of p38 Phosphorylation and Topoisomerase II Expression in the B-Cell Lymphoma Line Jiyoye by CD26/Dipeptidyl Peptidase IV Is Associated with Enhanced In vitro and In vivo Sensitivity to Doxorubicin

¹ Department of Lymphoma/Myeloma, University of Texas M.D. Anderson Cancer Center, Houston, Texas and ² Department of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan

Requests for reprints: Nam H. Dang, Department of Lymphoma/Myeloma, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 429, Houston, TX 77030. Phone: 713-792-2860; Fax: 713-794-5656. E-mail: nhdang{at}mail.mdanderson.org.

CD26 is a M_r 110,000 surface-bound glycoprotein with diverse functional properties, including having a key role in normal T-cell physiology and the development of certain cancers. In this article, we show that surface expression of CD26, especially its intrinsic dipeptidyl peptidase IV (DPPIV) enzyme activity, results in enhanced topoisomerase II level in the B-cell line Jiyoye and subsequent in vitro sensitivity to doxorubicin-induced apoptosis. In addition, we show that expression of CD26/DPPIV is associated with increased phosphorylation of p38 and its upstream regulators mitogen-activated protein kinase kinase 3/6 and apoptosis signal-regulating kinase 1 and that p38 signaling pathway plays a role in the regulation of topoisomerase II expression. Besides demonstrating that CD26 effect on topoisomerase II and doxorubicin sensitivity is applicable to cell lines of both B-cell and T-cell lineages, the potential clinical implication of our work lies with the fact that we now show for the first time that our in vitro results can be extended to a severe combined immunodeficient mouse model. Our findings that CD26 expression can be an in vivo marker of tumor sensitivity to doxorubicin treatment may lead to future treatment strategies targeting CD26/DPPIV for selected human cancers in the clinical setting. Our article thus characterizes the biochemical linkage among CD26, p38, and topoisomerase II while providing evidence that CD26-associated topoisomerase II expression results in greater in vitro and in vivo tumor sensitivity to the antineoplastic agent doxorubicin.

Key Words: CD26/DPPIV • p38 • topoisomerase II • doxorubicin • Jiyoye

This article has been cited by other articles:

				T. Inamoto, T. Yamada, K. Ohnuma, S. Kina, N. Takahashi, T. Yamochi, S. Inamoto, Y. Katsuoka, O. Hosono, H. Tanaka, et al. Humanized Anti-CD26 Monoclonal Antibody as a Treatment for Malignant Mesothelioma Tumors Clin. Cancer Res., July 15, 2007; 13(14): 4191 - 4200. [Abstract] [Full Text] [PDF]

				D. J. Drucker Dipeptidyl Peptidase-4 Inhibition and the Treatment of Type 2 Diabetes: Preclinical biology and mechanisms of action Diabetes Care, June 1, 2007; 30(6): 1335 - 1343. [Full Text] [PDF]

				T. Inamoto, T. Yamochi, K. Ohnuma, S. Iwata, S. Kina, S. Inamoto, M. Tachibana, Y. Katsuoka, N. H. Dang, and C. Morimoto Anti-CD26 Monoclonal Antibody-Mediated G1-S Arrest of Human Renal Clear Cell Carcinoma Caki-2 Is Associated with Retinoblastoma Substrate Dephosphorylation, Cyclin-Dependent Kinase 2 Reduction, p27kip1 Enhancement, and Disruption of Binding to the Extracellular Matrix. Clin. Cancer Res., June 1, 2006; 12(11): 3470 - 3477. [Abstract] [Full Text] [PDF]

				T. Sato, T. Yamochi, T. Yamochi, U. Aytac, K. Ohnuma, K. S. McKee, C. Morimoto, and N. H. Dang CD26 Regulates p38 Mitogen-Activated Protein Kinase-Dependent Phosphorylation of Integrin {beta}1, Adhesion to Extracellular Matrix, and Tumorigenicity of T-Anaplastic Large Cell Lymphoma Karpas 299 Cancer Res., August 1, 2005; 65(15): 6950 - 6956. [Abstract] [Full Text] [PDF]