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The activation of mTOR by human T-cell leukemia virus type 1 Tax is important for the transformation of mouse T cells to IL-2-independent growth.
MedLine Citation:
PMID:  22010857     Owner:  NLM     Status:  Publisher    
Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia (ATL), and it immortalizes and transforms human T cells in both interleukin(IL)-2-dependent and independent manners, respectively. HTLV-1 encodes Tax, which plays crucial roles in HTLV-1-mediated immortalization and transformation of human T cells. A previous study showed that Tax can transform a mouse T cell line, CTLL-2, from having IL-2-dependent growth to IL-2 independent growth. Given that the Akt/mTOR pathway is essential for IL-2-induced cell growth in T cells, we examined whether the Akt/mTOR pathway is involved in Tax-induced transformation to IL-2-independent growth. The stable and transient expression of Tax in CTLL-2 induced the phosphorylation of RPS6 and p70S6 kinase (S6K), downstream targets of the mTOR kinase, whereas that of Akt was only minimally induced. Studies with Tax mutants indicated that the activation of mTOR by Tax was correlated with the transformation of CTLL-2 cells to IL-2-independent growth. Rapamycin, an inhibitor of mTOR kinase, reduced the growth of Tax-transformed CTLL-2 cells. Moreover, the transduction of a constitutively active form of Akt in the CTLL-2 cells also induced IL-2-independent growth. Like CTLL-2/Tax, constitutive phosphorylation of S6K was detected in the absence of IL-2 in all of the HTLV-1-infected human T cell lines. These results suggest that Tax activates the mTOR pathway in T cells, and that this activation plays a crucial role in the growth of HTLV-1-infected T cells when a limited amount of IL-2 is available.
Manami Yoshita; Masaya Higuchi; Masahiko Takahashi; Masayasu Oie; Yuetsu Tanaka; Masahiro Fujii
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-19
Journal Detail:
Title:  Cancer science     Volume:  -     ISSN:  1349-7006     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101168776     Medline TA:  Cancer Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2011 Japanese Cancer Association.
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
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