An absolute role of the PKC-dependent NF-κB activation for induction of MMP-9 in hepatocellular carcinoma cells

Nasun Hah, Seung-Taek Lee

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72 Citations (Scopus)

Abstract

Matrix metalloproteinases (MMPs) play an important role in inflammation, tumor cell invasion, and metastasis. We found that phorbol-12-myristate-13-acetate (PMA)-stimulated invasion of the hepatocellular carcinoma (HCC) SNU-387 and SNU-398 cells and that PMA induced the secretion of MMP-9 in the cells, but did not induce the secretion of MMP-2. The PMA-induced MMP-9 secretion was abolished by treatment of a pan-protein kinase C (PKC) inhibitor, GF109203X, and an inhibitor of NF-κB activation, sulfasalazine, and partly inhibited by treatment of inhibitors of ERK pathway, PD98059 and U0126. In addition, the PMA-stimulated activation of the MMP-9 promoter was completely inhibited by a mutation of the NF-κB site within the MMP-9 promoter, but not completely by mutations of two AP-1 sites. Moreover, the MMP-9 induction by HGF and TNF-α was also completely inhibited by GF109203X and sulfasalazine, but not by PD98059 and U0126. These data demonstrate that the PKC-dependent NF-κB activation is absolute for MMP-9 induction and that the PKC-dependent ERK activation devotes to increase the expression level of MMP-9, in HCC cells.

Original languageEnglish
Pages (from-to)428-433
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume305
Issue number2
DOIs
Publication statusPublished - 2003 May 30

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Matrix Metalloproteinase 9
Protein Kinase C
Hepatocellular Carcinoma
Chemical activation
Cells
Acetates
Sulfasalazine
Mutation
MAP Kinase Signaling System
Protein C Inhibitor
Matrix Metalloproteinase 2
Transcription Factor AP-1
Protein Kinase Inhibitors
Matrix Metalloproteinases
Tumors
Neoplasm Metastasis
Inflammation
phorbol-12-myristate
Neoplasms

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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abstract = "Matrix metalloproteinases (MMPs) play an important role in inflammation, tumor cell invasion, and metastasis. We found that phorbol-12-myristate-13-acetate (PMA)-stimulated invasion of the hepatocellular carcinoma (HCC) SNU-387 and SNU-398 cells and that PMA induced the secretion of MMP-9 in the cells, but did not induce the secretion of MMP-2. The PMA-induced MMP-9 secretion was abolished by treatment of a pan-protein kinase C (PKC) inhibitor, GF109203X, and an inhibitor of NF-κB activation, sulfasalazine, and partly inhibited by treatment of inhibitors of ERK pathway, PD98059 and U0126. In addition, the PMA-stimulated activation of the MMP-9 promoter was completely inhibited by a mutation of the NF-κB site within the MMP-9 promoter, but not completely by mutations of two AP-1 sites. Moreover, the MMP-9 induction by HGF and TNF-α was also completely inhibited by GF109203X and sulfasalazine, but not by PD98059 and U0126. These data demonstrate that the PKC-dependent NF-κB activation is absolute for MMP-9 induction and that the PKC-dependent ERK activation devotes to increase the expression level of MMP-9, in HCC cells.",
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AU - Hah, Nasun

AU - Lee, Seung-Taek

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N2 - Matrix metalloproteinases (MMPs) play an important role in inflammation, tumor cell invasion, and metastasis. We found that phorbol-12-myristate-13-acetate (PMA)-stimulated invasion of the hepatocellular carcinoma (HCC) SNU-387 and SNU-398 cells and that PMA induced the secretion of MMP-9 in the cells, but did not induce the secretion of MMP-2. The PMA-induced MMP-9 secretion was abolished by treatment of a pan-protein kinase C (PKC) inhibitor, GF109203X, and an inhibitor of NF-κB activation, sulfasalazine, and partly inhibited by treatment of inhibitors of ERK pathway, PD98059 and U0126. In addition, the PMA-stimulated activation of the MMP-9 promoter was completely inhibited by a mutation of the NF-κB site within the MMP-9 promoter, but not completely by mutations of two AP-1 sites. Moreover, the MMP-9 induction by HGF and TNF-α was also completely inhibited by GF109203X and sulfasalazine, but not by PD98059 and U0126. These data demonstrate that the PKC-dependent NF-κB activation is absolute for MMP-9 induction and that the PKC-dependent ERK activation devotes to increase the expression level of MMP-9, in HCC cells.

AB - Matrix metalloproteinases (MMPs) play an important role in inflammation, tumor cell invasion, and metastasis. We found that phorbol-12-myristate-13-acetate (PMA)-stimulated invasion of the hepatocellular carcinoma (HCC) SNU-387 and SNU-398 cells and that PMA induced the secretion of MMP-9 in the cells, but did not induce the secretion of MMP-2. The PMA-induced MMP-9 secretion was abolished by treatment of a pan-protein kinase C (PKC) inhibitor, GF109203X, and an inhibitor of NF-κB activation, sulfasalazine, and partly inhibited by treatment of inhibitors of ERK pathway, PD98059 and U0126. In addition, the PMA-stimulated activation of the MMP-9 promoter was completely inhibited by a mutation of the NF-κB site within the MMP-9 promoter, but not completely by mutations of two AP-1 sites. Moreover, the MMP-9 induction by HGF and TNF-α was also completely inhibited by GF109203X and sulfasalazine, but not by PD98059 and U0126. These data demonstrate that the PKC-dependent NF-κB activation is absolute for MMP-9 induction and that the PKC-dependent ERK activation devotes to increase the expression level of MMP-9, in HCC cells.

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