Transactivation of human osteopontin promoter by human T-cell leukemia virus type 1-encoded Tax protein.
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.
Zhang
Jing
J
Research and Development Center, FUSO Pharmaceutical Industries, Ltd, Joto-ku, Osaka 536-8523, Japan. j-zhang@fuso-pharm.co.jp
Yamada
Osamu
O
Matsushita
Yoshihisa
Y
Chagan-Yasutan
Haorile
H
Hattori
Toshio
T
D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016356:Gene Products, tax / Q000378:metabolism / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation
D016356:Gene Products, tax; D018808:Transcription Factor AP-1; C514970:tax protein, Human T-lymphotrophic virus 1; D053495:Osteopontin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt