Document Detail


Transactivation of human osteopontin promoter by human T-cell leukemia virus type 1-encoded Tax protein.
MedLine Citation:
PMID:  19767100     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Osteopontin (OPN) is a cytokine that contributes substantially to the growth and metastasis in a wide spectrum of malignancies. We report here that OPN gene is transactivated by Tax protein of human T-cell leukemia virus type 1 (HTLV-1). Northern blot showed enhanced OPN gene expression in cells stably expressing Tax. Co-expression of Tax increased the reporter gene expression directed by OPN promoter. Tax-induced OPN activation was abrogated by treatment with LY294002 (PI3K inhibitor) or co-transfection with AKT siRNA, suggesting PI3K/AKT pathway is involved in Tax-mediated transactivation. Reporter assay with deletion mutants showed that the 5'-partial sequence between -765 and -660 of the OPN promoter is the region responsive to Tax, and further, disrupting the AP-1 site within this region abolished the OPN induction by Tax, indicating that Tax activation of OPN promoter is likely mediated by AP-1 site. This study suggests that OPN is one of the downstream mediators of aberrantly activated PI3K/AKT signaling by Tax, which may partially contribute to HTLV-1-associated leukemogenesis.
Authors:
Jing Zhang; Osamu Yamada; Yoshihisa Matsushita; Haorile Chagan-Yasutan; Toshio Hattori
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-19
Journal Detail:
Title:  Leukemia research     Volume:  34     ISSN:  1873-5835     ISO Abbreviation:  Leuk. Res.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-04-23     Completed Date:  2010-06-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7706787     Medline TA:  Leuk Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  763-8     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Ltd. All rights reserved.
Affiliation:
Research and Development Center, FUSO Pharmaceutical Industries, Ltd, Joto-ku, Osaka 536-8523, Japan. j-zhang@fuso-pharm.co.jp
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / metabolism,  physiology
Base Sequence
Binding Sites
Carcinoma, Hepatocellular / genetics,  metabolism,  pathology
Cell Line, Tumor
Cell Transformation, Viral / genetics
Gene Expression Regulation, Neoplastic
Gene Products, tax / metabolism,  physiology*
Human T-lymphotropic virus 1 / genetics,  physiology
Humans
Liver Neoplasms / genetics,  metabolism,  pathology
Osteopontin / genetics*,  metabolism
Promoter Regions, Genetic / physiology
Proto-Oncogene Proteins c-akt / metabolism,  physiology
Signal Transduction / genetics
Transcription Factor AP-1 / metabolism
Transcriptional Activation*
Chemical
Reg. No./Substance:
0/Gene Products, tax; 0/Transcription Factor AP-1; 0/tax protein, Human T-lymphotrophic virus 1; 106441-73-0/Osteopontin; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Alternative splicing of hMLH1 in childhood acute lymphoblastic leukaemia and characterisation of the...
Next Document:  Child sexual abuse consequences in community samples of Latino and European American adolescents.