RRC ID 34788
Author Yoshita M, Higuchi M, Takahashi M, Oie M, Tanaka Y, Fujii M.
Title Activation of mTOR by human T-cell leukemia virus type 1 Tax is important for the transformation of mouse T cells to interleukin-2-independent growth.
Journal Cancer Sci
Abstract Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia, and it immortalizes and transforms human T cells in both an interleukin (IL)-2-dependent and -independent manner. 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 p70S6 kinase and ribosomal protein S6, 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 p70S6 kinase 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.
Volume 103(2)
Pages 369-74
Published 2012-2-1
DOI 10.1111/j.1349-7006.2011.02123.x
PMID 22010857
MeSH Animals Cell Line Cell Line, Tumor Cell Proliferation / drug effects Cell Transformation, Viral* Gene Products, tax / genetics Gene Products, tax / metabolism* Human T-lymphotropic virus 1* Humans Interleukin-2 / metabolism Mice Mutation Oncogene Protein v-akt / metabolism Phosphorylation Ribosomal Protein S6 Kinases, 70-kDa / metabolism Sirolimus / pharmacology T-Lymphocytes / physiology* T-Lymphocytes / virology* TOR Serine-Threonine Kinases / antagonists & inhibitors TOR Serine-Threonine Kinases / metabolism*
IF 4.966
Times Cited 13
DNA material CSII-EF-RfA (RDB04387) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394).