title: Overexpression of caveolin-1 in adult T-cell leukemia.
abstract: Caveolin-1 is implicated in the regulation of signal pathways. Adult T-cell leukemia (ATL) is a T-cell malignancy causatively associated with human T-cell leukemia virus type 1 (HTLV-1). To determine the role of caveolin-1 in leukemogenesis, we examined caveolin-1 expression levels in HTLV-1-infected T-cell lines and ATL cells. These cells expressed high levels of caveolin-1 compared with uninfected T-cell lines and normal peripheral blood mononuclear cells (PBMCs). Caveolin-1-positive ATL cells were detected in ATL lymph nodes and skin lesions, and caveolin-1 was also detected in the plasma of patients with ATL. Infection of a human T-cell line, an epithelial cell line, and normal PBMCs with HTLV-1 induced caveolin-1 expression. The viral protein Tax transcriptionally activated caveolin-1 gene through nuclear factor-kappaB and cAMP response element binding protein signal pathways. HTLV-1-infected T-cell lines, and ATL cells are known to be resistant to transforming growth factor beta (TGF-beta)-induced growth inhibition. Caveolin-1 was colocalized with TGF-beta type I receptor in HTLV-1-infected T-cell lines and suppressed TGF-beta signaling. Caveolin-1 knockdown in an HTLV-1-infected T-cell line exhibited susceptibility to TGF-beta. Thus, we describe a new function for Tax, repression of TGF-beta signaling through caveolin-1 expression, which may play a critical role in ATL leukemogenesis.
authors.affiliation: Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sawada
authors.forename: Chie
authors.initials: C
authors.lastname: Ishikawa
authors.forename: Hiroe
authors.initials: H
authors.lastname: Tanji
authors.forename: Sawako
authors.initials: S
authors.lastname: Nakachi
authors.forename: Masachika
authors.initials: M
authors.lastname: Senba
authors.forename: Taeko
authors.initials: T
authors.lastname: Okudaira
authors.forename: Jun-Nosuke
authors.initials: JN
authors.lastname: Uchihara
authors.forename: Naoya
authors.initials: N
authors.lastname: Taira
authors.forename: Kazuiku
authors.initials: K
authors.lastname: Ohshiro
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uezato
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Ken
authors.initials: K
authors.lastname: Sasai
authors.forename: Boudewijn M T
authors.initials: BM
authors.lastname: Burgering
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duc Dodon
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujii
authors.forename: Hajime
authors.initials: H
authors.lastname: Sunakawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Mori
mesh_terms: D000328:Adult; D051242:Caveolin 1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015533:Transcriptional Activation / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I