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 Imaizumi, Y. Articles by Matsuyama, T. Search for Related Content PubMed PubMed Citation Articles by Imaizumi, Y. Articles by Matsuyama, T.

Expression of the c-Met Proto-Oncogene and Its Possible Involvement in Liver Invasion in Adult T-cell Leukemia¹

Divisions of Cytokine Signaling [Y. I., H. M., To. K., K. Y., T. M.] and Endothelial Cell Biology [S. K.], Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Medical Sciences and Departments of Laboratory Medicine [Y. Y.], Hematology, Atomic Disease Institute [Y. I., M. T.], and Histology and Cell Biology [Y. H., Ta. K.] and Second Department of Pathology [T. T.], Nagasaki University School of Medicine, Nagasaki 852-8523; Departments of Infectious Disease and Immunology, Okinawa-Asia Research Center of Medical Science [Y. T.], and Virology [N. M.], Faculty of Medicine, University of the Ryukyus, Okinawa 903-0215; and Department of Medicine, City of Sasebo General Hospital, Sasebo 857-8511 [S. I.], Japan

c-Met is a tyrosine kinase receptor for hepatocyte growth factor and suggested to be involved in oncogenesis ormetastatic phenotypes in many malignancies. Adult T-cell leukemia (ATL) is a neoplasia characterized by massive invasion of the leukemic cells into various organs. Recently, we have reported frequent hepatic involvement and the relationship between liver invasion and the poor prognosis in ATL. In the present study, we investigated the expression of c-Met in ATL cells and its relation to liver dysfunction. In three of four human T-cell lymphotrophic virus-I-positive T-cell lines, c-Met was expressed both at mRNA and protein levels, whereas it was not expressed in human T-cell lymphoma virus-I-negative T-cell lines. The expressed c-Met should be functional, because hepatocyte growth factor could induce the autophosphorylation of c-Met. Although the viral-transactivating protein Tax has been shown to be involved in the deregulated expression of cellular genes, Tax mRNA was not detected in c-Met mRNA-expressed cell lines. From freshly isolated peripheral blood mononuclear cells, the expression of c-Met mRNA was detected in 10 of 16 ATL patients but not from healthy individuals. Finally, serum transaminase levels were significantly increased in c-Met-positive ATL cases, and all of the infiltrated c-Met-positive cells into liver were shown to be multilobularly nucleated phenotype. Taken together, these data suggest for the first time that c-Met is involved in the liver invasive phenotype of ATL.

This article has been cited by other articles:

				K. Okunishi, M. Dohi, K. Fujio, K. Nakagome, Y. Tabata, T. Okasora, M. Seki, M. Shibuya, M. Imamura, H. Harada, et al. Hepatocyte Growth Factor Significantly Suppresses Collagen-Induced Arthritis in Mice J. Immunol., October 15, 2007; 179(8): 5504 - 5513. [Abstract] [Full Text] [PDF]

				B. Accordi, S. Pillozzi, M. C. Dell'Orto, G. Cazzaniga, A. Arcangeli, G. t. Kronnie, and G. Basso Hepatocyte Growth Factor Receptor c-MET Is Associated with FAS and When Activated Enhances Drug-induced Apoptosis in Pediatric B Acute Lymphoblastic Leukemia with TEL-AML1 Translocation J. Biol. Chem., October 5, 2007; 282(40): 29384 - 29393. [Abstract] [Full Text] [PDF]

				K. Okunishi, M. Dohi, K. Nakagome, R. Tanaka, S. Mizuno, K. Matsumoto, J.-i. Miyazaki, T. Nakamura, and K. Yamamoto A Novel Role of Hepatocyte Growth Factor as an Immune Regulator through Suppressing Dendritic Cell Function J. Immunol., October 1, 2005; 175(7): 4745 - 4753. [Abstract] [Full Text] [PDF]