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Title :A modified version of galectin-9 suppresses cell growth and induces apoptosis of human T-cell leukemia virus type I-infected T-cell lines.
Authors :Okudaira, Taeko
Hirashima, Mitsuomi
Ishikawa, Chie
Makishi, Shoko
Tomita, Mariko
Matsuda, Takehiro
Kawakami, Hirochika
Taira, Naoya
Ohshiro, Kazuiku
Masuda, Masato
Takasu, Nobuyuki
Mori, Naoki
Issue Date :2-Feb-2007
Abstract :ATL is a fatal malignancy of T lymphocytes caused by HTLV-I infection and remains incurable. Galectins are a family of animal lectins that function both extracellularly (by interacting with cell surface and extracellular matrix glycoproteins and glycolipids) and intracellularly (by interacting with cytoplasmic and nuclear proteins) to modulate signaling pathways. We found that protease-resistant galectin-9 by modification of its linker peptide, hG9NC(null), prevented cell growth of HTLV-I-infected T-cell lines and primary ATL cells. The suppression of cell growth was inhibited by lactose, but not by sucrose, indicating that β-galactoside binding is essential for hG9NC(null)-induced cell growth suppression. hG9NC(null) induced cell cycle arrest by reducing the expression of cyclin D1, cyclin D2, cyclin B1, Cdk1, Cdk4, Cdk6, Cdc25C and c-Myc, and apoptosis by reducing the expression of XIAP, c-IAP2 and survivin. Most of these genes are regulated by NF-κB, which plays a critical role in oncogenesis by HTLV-I. hG9NC(null) suppressed IκBα phosphorylation, resulting in suppression of NF-κB. Most importantly, treatment with hG9NC(null) (6.7 mg/kg injected intraperitoneally every day) reduced tumor formation from an HTLV-I-infected T-cell line when these cells were inoculated subcutaneously into SCID mice. Our results suggest that hG9NC(null) could be a suitable agent for the management of ATL.
Type Local :雑誌掲載論文
ISSN :0020-7136
Publisher :Wiley-Liss, Inc.
URI :http://hdl.handle.net/20.500.12000/484
Citation :International Journal of Cancer Vol.120 no.10 p.2251 -2261
Appears in Collections:Peer-reviewed Journal Articles (Faculty of Medicine)

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