title: p21WAF1 mediates the IL-15-induced migration and invasion of human bladder cancer 5637 cells via the ERK1/2/NF-κB/MMP-9 pathway.
abstract: Interleukin-15 (IL-15) functions as a key regulator for the proliferation, differentiation, and activation of lymphocytes. However, the role of IL-15 in cancer biology is not yet understood. In the present study, IL-15 treatment stimulated the wound-healing migration and invasion of bladder cancer 5637 cells, without altering the proliferation of the cells. Treatment of 5637 cells with IL-15 resulted in the promotion of the MMP-9 expression and the activation of NF-κB binding, which is a functional transcription factor that activates MMP-9 expression. In addition, IL-15 induced the activation of ERK1/2. ERK inhibitor U0126 suppressed the migration, invasion, MMP-9 expression, and NF-κB binding activity in IL-15-treated 5637 cells. In addition, the cell-cycle inhibitor p21WAF1 was induced by the addition of IL-15. Finally, the siRNA-mediated knockdown of p21WAF1 attenuated the IL-15-induced stimulation of migration, invasion, ERK1/2 activation, MMP-9 expression, and NF-κB binding activation in 5637 cells. Our results suggest that p21WAF1 regulated NF-κB-mediated MMP-9 expression via the activation of ERK1/2, which resulted in the migration and invasion of 5637 cells treated with IL-15. These unexpected results suggest a potential role for IL-15 with respect to the progression of bladder cancer.
authors: School of Food Science and Technology, Chung-Ang University, Ansung 456-756, Korea.
authors: Sung Lyea
authors: SL
authors: Park
authors: Personalized Tumor Engineering Research Center, Department of Urology, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
authors: Wun-Jae
authors: WJ
authors: Kim
authors: School of Food Science and Technology, Chung-Ang University, Ansung 456-756, Korea. Electronic address: sumoon66@dreamwiz.com.
authors: Sung-Kwon
authors: SK
authors: Moon
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009570:Nitriles / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D002070:Butadienes; D019409:Interleukin-15; D016328:NF-kappa B; D009570:Nitriles; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9
keywords: Bladder cancer cells; IL-15; Invasion; Migration; p21WAF1