Activation of matrix metalloproteinase-9 by TNF-α in human urinary bladder cancer HT1376 cells: The role of MAP kinase signaling pathways

Abstract

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-α (TNF-α) stimulated the secretion of MMP-9 in HT1376 cells, as shown by zymography and immunoblot analysis. At the level of transcription, TNF-α also stimulated 5'-flanking promoter activity of MMP-9. Transcription factor NF-κB, AP-1 and Sp-1 binding sites were identified by a gel shift assay to be cis-elements for TNF-α activation of the MMP-9 promoter. TNF-α activates multiple signaling pathways in HT1376 cells, including the extracellular signalregulated kinase (ERK1/2), p38 MAP kinase and JNK pathways. Chemical inhibitors, which specifically inhibit each of these TNF-α-activated pathways, were used to examine the signaling pathways involved in TNF-α-mediated MMP-9 expression. The ERK1/2 inhibitor, U0126 and the p38 MAP kinase inhibitor, SB203580, significantly downregulated TNF-α-induced MMP-9 expression and promoter activity. The transactivation of TNF-α-stimulated NF-κB, AP-1 and Sp-1 were inhibited by U0126 and SB203580 treatment. In conclusion, the findings of the present study indicate that TNF-α 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-κB, AP-1 and Sp-1.

Transcriptional Repression of Caveolin-1 (CAV1) Gene Expression by GATA-6 in Bladder Smooth Muscle Hypertrophy in Mice and Human Beings

“…56 Among the transcription factors that were studied at promoter pull-down analysis with the nuclear extract from murine sham and PBOO BSM tissues, transcription factor Ets-2 is overexpressed in human bladder cancer, 57 and SP-1 regulates tumor necrosis factor-␣-induced MMP-9 expression through ERK1/2 and p38 MAP kinase in bladder cancer cells. 58 However, in murine and human obstructed BSM tissues, Ets-2 and SP-1 are not overexpressed. Moreover, E2F and Sp-1 did not interact with murine CAV1 promoter as revealed at promoter pulldown analysis.…”

Interleukin-20 Promotes Migration of Bladder Cancer Cells through Extracellular Signal-regulated Kinase (ERK)-mediated MMP-9 Protein Expression Leading to Nuclear Factor (NF-κB) Activation by Inducing the Up-regulation of p21WAF1 Protein Expression *

“…In this study, we focused on the regulatory roles of MMP-9 in IL-20-treated bladder cancer cells. The MMP-9 gene promoter contains several transcription factors, including NF-B, Sp-1, and AP-1 that are verified as binding sites in humans and mice (7)(8)(9)(10)(11)27). We first examined whether IL-20 can induce the activation of NF-B, Sp-1, and AP-1 in bladder cancer cells.…”

“…Previous studies have shown that MMP-9 supports crucial roles in the progression of bladder tumor in vitro and in vivo (4). Many studies have shown that growth factors and cytokines can stimulate MMP-9 expression in several types of cells (7)(8)(9)(10). Further studies have demonstrated that the transcription factors NF-B, Sp-1, and AP-1 are key transcriptional regulators responsible for the induction of MMP-9 in cancer cells (7)(8)(9)(10)(11).…”

Cordycepin suppresses TNF‐alpha‐induced invasion, migration and matrix metalloproteinase‐9 expression in human bladder cancer cells

“…Previous studies have indicated that TNF-α is a potent activator of MMP-9 in bladder cancer cells (Lee et al, 2008a(Lee et al, , 2008bShin et al, 2000). TNF-α induces MMP-9 expression in several tumor cell types by activation of the transcription factors NF-κB and AP-1 (Bond et al, 1998;Lee et al, 2008aLee et al, , 2008b.…”

“…However, based on previous reports, it is clear that several classes of proteins are involved in determining bladder cancer risk (Sier et al, 2000). Many studies have shown that MMP-9 is associated with invasiveness and bladder cancer progression (Davies et al, 1993;Lee et al, 2008aLee et al, , 2008bNutt et al, 2003;Shin et al, 2000).…”