| Transactivation of human osteopontin promoter by human T-cell leukemia virus type 1-encoded Tax protein. | |
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MedLine Citation:
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PMID: 19767100 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Jing Zhang; Osamu Yamada; Yoshihisa Matsushita; Haorile Chagan-Yasutan; Toshio Hattori |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-09-19 |
Journal Detail:
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Title: Leukemia research Volume: 34 ISSN: 1873-5835 ISO Abbreviation: Leuk. Res. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-04-23 Completed Date: 2010-06-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7706787 Medline TA: Leuk Res Country: England |
Other Details:
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Languages: eng Pagination: 763-8 Citation Subset: IM |
Copyright Information:
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Copyright 2009 Elsevier Ltd. All rights reserved. |
Affiliation:
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Research and Development Center, FUSO Pharmaceutical Industries, Ltd, Joto-ku, Osaka 536-8523, Japan. j-zhang@fuso-pharm.co.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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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:
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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
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