Document Detail

HTLV-I Tax-dependent and -independent events associated with immortalization of human primary T lymphocytes.
MedLine Citation:
PMID:  20093405     Owner:  NLM     Status:  MEDLINE    
Human T-cell leukemia virus type I (HTLV-I)-associated malignancies are seen in a small percentage of infected persons. Although in vitro immortalization by HTLV-I virus is very efficient, we report that Tax has poor oncogenic activity in human primary T cells and that immortalization by Tax is rare. Sustained telomerase activity represents one of the oncogenic steps required for Tax-mediated immortalization. Tax expression was required for the growth of primary T cells, but was not sufficient to propel T cells into cell cycle in the absence of exogenous interleukin-2 (IL-2). Tax was sufficient to activate the phosphoinositide-3 kinase (PI3K)/Akt pathway as shown by down regulation of Src homology phosphatase-1 and increased phosphorylation of Akt. We also found disruption of putative tumor suppressors IL-16 and translocated promoter region (TPR) in Tax-immortalized and HTLV-I-transformed cell lines. Our results confirmed previous observations that Tax activates the anaphase-promoting complex. However, Tax did not affect the mitotic spindle checkpoint, which was also functional in HTLV-I-transformed cells. These data provide a better understanding of Tax functions in human T cells, and highlight the limitations of Tax, suggesting that other viral proteins are key to T-cell transformation and development of adult T-cell leukemia.
Marcia Bellon; Hicham H Baydoun; Yuan Yao; Christophe Nicot
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-01-21
Journal Detail:
Title:  Blood     Volume:  115     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-26     Completed Date:  2010-04-13     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2441-8     Citation Subset:  AIM; IM    
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MeSH Terms
Cell Aging / physiology
Cell Division / drug effects,  physiology
Cell Line, Transformed
Cell Transformation, Viral / physiology*
Chromosome Aberrations
Gene Products, tax / genetics*
Genomic Instability / physiology
Human T-lymphotropic virus 1 / genetics*
Interleukin-2 / pharmacology
Lymphoma, T-Cell / pathology,  virology*
T-Lymphocytes / pathology,  virology*
Telomere / physiology
Grant Support
Reg. No./Substance:
0/Gene Products, tax; 0/Interleukin-2; 0/tax protein, Human T-lymphotrophic virus 1

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