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Activation of matrix metalloproteinase-9 by TNF-α in human urinary bladder cancer HT1376 cells: The role of MAP kinase signaling pathways
- Source :
- Oncology Reports.
- Publication Year :
- 2008
- Publisher :
- Spandidos Publications, 2008.
-
Abstract
- The expression of matrix metalloproteinase-9 (MMP-9) has been implicated in tumor invasion and metastasis. In this study, the factors and signaling pathways that are involved in the regulation of the MMP-9 expression were examined in urinary bladder cancer HT1376 cells. Tumor necrosis factor-alpha (TNF-alpha) stimulated the secretion of MMP-9 in HT1376 cells, as shown by zymography and immunoblot analysis. At the level of transcription, TNF-alpha also stimulated 5'-flanking promoter activity of MMP-9. Transcription factor NF-kappaB, AP-1 and Sp-1 binding sites were identified by a gel shift assay to be cis-elements for TNF-alpha activation of the MMP-9 promoter. TNF-alpha activates multiple signaling pathways in HT1376 cells, including the extracellular signal-regulated kinase (ERK1/2), p38 MAP kinase and JNK pathways. Chemical inhibitors, which specifically inhibit each of these TNF-alpha-activated pathways, were used to examine the signaling pathways involved in TNF-alpha-mediated MMP-9 expression. The ERK1/2 inhibitor, U0126 and the p38 MAP kinase inhibitor, SB203580, significantly down-regulated TNF-alpha-induced MMP-9 expression and promoter activity. The transactivation of TNF-alpha-stimulated NF-kappaB, AP-1 and Sp-1 were inhibited by U0126 and SB203580 treatment. In conclusion, the findings of the present study indicate that TNF-alpha induces MMP-9 expression in HT1376 cells by activating transcription factors, which are involved in the ERK1/2- and p38 MAP kinase-mediated control of MMP-9 regulation, namely, NF-kappaB, AP-1 and Sp-1.
- Subjects :
- Cancer Research
medicine.medical_specialty
MAP kinase kinase kinase
Kinase
Activating transcription factor
NF-κB
General Medicine
Biology
Cell biology
Transactivation
chemistry.chemical_compound
Endocrinology
Oncology
chemistry
Internal medicine
Mitogen-activated protein kinase
medicine
biology.protein
Signal transduction
Transcription factor
Subjects
Details
- ISSN :
- 17912431 and 1021335X
- Database :
- OpenAIRE
- Journal :
- Oncology Reports
- Accession number :
- edsair.doi...........fa300ee12989ccd24550d5ffae928a9c