title: Expression of the c-Met proto-oncogene and its possible involvement in liver invasion in adult T-cell leukemia.
abstract: 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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Medical Sciences, Nagasaki 852-8523, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Imaizumi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Murota
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kanda
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hishikawa
authors.forename: Takehiko
authors.initials: T
authors.lastname: Koji
authors.forename: Takashi
authors.initials: T
authors.lastname: Taguchi
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Yamada
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ikeda
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kohno
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Mori
authors.forename: Masao
authors.initials: M
authors.lastname: Tomonaga
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Matsuyama
mesh_terms: D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D016356:Gene Products, tax / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D010641:Phenotype; D010766:Phosphorylation; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000637:Transaminases / Q000097:blood; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D016356:Gene Products, tax; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D000637:Transaminases; D019859:Proto-Oncogene Proteins c-met