Signal transducer and activator of transcription 3 upregulates interleukin-8 expression at the level of transcription in human melanoma cells

被引:14
作者
Oka, Masahiro [1 ]
Sakaguchi, Masanobu
Okada, Taro [2 ]
Nagai, Hiroshi
Ozaki, Michitaka [3 ]
Yoshioka, Toyo [4 ]
Inoue, Hiroshi [5 ]
Mukaida, Naofumi [6 ,7 ]
Kikkawa, Ushio [8 ]
Nishigori, Chikako
机构
[1] Kobe Univ, Grad Sch Med, Div Dermatol, Dept Internal Related,Chuo Ku, Kobe, Hyogo 6500017, Japan
[2] Kobe Univ, Grad Sch Med, Div Biochem, Dept Mol & Cellular Biol, Kobe, Hyogo 6500017, Japan
[3] Hokkaido Univ, Sch Med, Dept Mol Surg, Sapporo, Hokkaido 060, Japan
[4] Kobe Univ, Grad Sch Med, Div Diabet Metab & Endocrinol, Dept Internal Related, Kobe, Hyogo 6500017, Japan
[5] Kanazawa Univ, Frontier Sci Org, Kanazawa, Ishikawa, Japan
[6] Kanazawa Univ, Canc Res Inst, Ctr Target Drug Dev, Kanazawa, Ishikawa 920, Japan
[7] Kanazawa Univ, Div Mol Bioregulat, Kanazawa, Ishikawa 920, Japan
[8] Kobe Univ, Biosignal Res Ctr, Kobe, Hyogo 6500017, Japan
关键词
IL-8; luciferase assay; melanoma; STAT3; transcription; EPIDERMAL-GROWTH-FACTOR; KAPPA-B ACTIVATION; MALIGNANT-MELANOMA; CHEMOTACTIC CYTOKINES; METASTATIC MELANOMA; STAT3; ACTIVATION; REQUIREMENT; INDUCTION; PATHWAY; BINDING;
D O I
10.1111/j.1600-0625.2009.00972.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Many melanoma cells continuously produce interleukin-8 (IL-8). The involvement of signal transducer and activator of transcription 3 (STAT3) in the constant production of IL-8 in melanoma cells was examined. The level of IL-8 production correlated well with that of the phosphorylated (activated) STAT3 in six human melanoma cell lines. Introduction of the constitutively activated form of STAT3 (STAT3-C) into WM35 melanoma cells, that show low levels of IL-8 and phosphorylated STAT3, enhanced IL-8 production. Knockdown of STAT3 suppressed IL-8 production in WM1205Lu cells that contain a high level of IL-8 accompanied by STAT3 phosphorylation. Introduction of STAT3-C markedly increased the luciferase activity in WM1205Lu cells transfected with reporter vectors linked to the 5'-flanking region of the IL-8 gene from -546 to +44 base pair (bp) and from -272 to +44 bp, but not in cells expressing reporter plasmids from -133 to +44 bp and from -98 to +44 bp. These results indicate that the upregulation of IL-8 production is caused by constitutive STAT3 activation at the level of gene transcription in melanoma cells.
引用
收藏
页码:E50 / E55
页数:6
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