title: p27KIP1 is involved in ERK1/2-mediated MMP-9 expression via the activation of NF-κB binding in the IL-7-induced migration and invasion of 5637 cells.
abstract: Interleukin-7 (IL-7) plays a pivotal role in the development and survival of lymphocytes, but its role in cancer cell responses remains unexplained. In this study, IL-7 treatment resulted in a significant induction in the wound-healing migration and Matrigel invasion of the 5637 bladder cancer cells, but it did not result in cell proliferation. In addition, IL-7 treatment strongly induced MMP-9 expression, and increased the binding activation of NF-κB and AP-1 motifs, the important transcription factors that regulate MMP-9 expression. Moreover, the treatment of 5637 cells with IL-7 stimulated the phosphorylation of ERK1/2. U0126, an ERK1/2-specific inhibitor, blocked IL-7-induced cell migration and invasion, and also suppressed the expression of MMP-9 in the presence of IL-7. Inhibition of the ERK1/2 function consistently reversed the binding activity of NF-κB without altering AP-1 activation in IL-7-stimulated cells. Among the cell cycle regulators examined, only the expression of the cell cycle inhibitor p27KIP1 was induced by IL-7. Moreover, the inhibition of p27KIP1 by small interfering RNA (siRNA) abolished the migration, invasion and phosphorylation of ERK1/2, the expression of MMP-9, and the binding activity of the NF-κB motif in IL-7-stimulated 5637 cells. These results demonstrated that the cell cycle inhibitor p27KIP1 is involved in ERK1/2-mediated MMP-9 expression via activation of the NF-κB binding motif, which leads to the migration and invasion of bladder cancer cells induced by IL-7. These novel results could help explain the migration and invasion of bladder tumor cells.
authors: School of Food Science and Technology, Chung-Ang University, Ansung 456-756, Republic of Korea.
authors: Sung Lyea
authors: SL
authors: Park
authors: Personalized Tumor Engineering Research Center, Department of Urology, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors: Eo-Jin
authors: EJ
authors: Lee
authors: Personalized Tumor Engineering Research Center, Department of Urology, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors: Wun-Jae
authors: WJ
authors: Kim
authors: School of Food Science and Technology, Chung-Ang University, Ansung 456-756, Republic of Korea.
authors: Sung-Kwon
authors: SK
authors: Moon
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1 / Q000096:biosynthesis; D001749:Urinary Bladder Neoplasms / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects
chemical_list: C436291:CDKN1B protein, human; C508605:IL7 protein, human; D015851:Interleukin-7; D016328:NF-kappa B; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9