Overexpression of caveolin-1 in adult T-cell leukemia.
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.
Sawada
Shigeki
S
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
Ishikawa
Chie
C
Tanji
Hiroe
H
Nakachi
Sawako
S
Senba
Masachika
M
Okudaira
Taeko
T
Uchihara
Jun-Nosuke
JN
Taira
Naoya
N
Ohshiro
Kazuiku
K
Yamada
Yasuaki
Y
Tanaka
Yuetsu
Y
Uezato
Hiroshi
H
Ohshima
Koichi
K
Sasai
Ken
K
Burgering
Boudewijn M T
BM
Duc Dodon
Madeleine
M
Fujii
Masahiro
M
Sunakawa
Hajime
H
Mori
Naoki
N
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
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