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Regulation of MMP-9 (type IV collagenase) production and invasiveness in gliomas by the extracellular signal-regulated kinase and jun amino-terminal kinase signaling cascades

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Abstract

Our previous studies have shown that MMP-9 levels are significantly elevated during the progression of human gliomas. In the current study, we examined the role of JNK- and ERK-dependent signaling modules in the regulation of MMP-9 production and the invasive behavior of the human glioblastoma cell line SNB19, in which JNK/ERK1 is constitutively activated. SNB19 cells that were transfected with dominant-negative JNK, MEKK, and ERK1 expression vectors showed reduced MMP-9 promoter activity. In addition, conditioned medium collected from SNB19 cells transfected with these expression vectors showed diminished MMP-9 activity in the presence of phorbol myristate acetate, as determined by gelatin zymography. The cotransfection of SNB19 cells with kinase-deficient c-raf also diminished MMP-9 promoter activity. Further, in the presence of a specific inhibitor of MEKK (PD098059), the Matrigel invasion assay showed the invasiveness of dominant-negative SNB19 cells transfected with dominant-negative JNK1 or ERK1 to be remarkably reduced. In conclusion, our studies showed for the first time that MMP-9 production and the invasive behavior of SNB19 cells are regulated by JNK- and ERK-dependent signaling modules and that interfering with either of the pathways reduces invasiveness.

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Authors and Affiliations

  1. Departments of Neurosurgery, USA

    Sajani S. Lakka, Francis Ali-Osman & Jasti S. Rao

  2. Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA

    Sushma L. Jasti, Anthanassios P. Kyritsis & W.K. Alfred Yung

  3. Insititute for Molecular Medicine, Huntington Beach, California, USA

    Garth L. Nicolson

Authors
  1. Sajani S. Lakka
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  2. Sushma L. Jasti
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  3. Anthanassios P. Kyritsis
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  7. Jasti S. Rao
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Lakka, S.S., Jasti, S.L., Kyritsis, A.P. et al. Regulation of MMP-9 (type IV collagenase) production and invasiveness in gliomas by the extracellular signal-regulated kinase and jun amino-terminal kinase signaling cascades. Clin Exp Metastasis 18, 245–252 (2000). https://doi.org/10.1023/A:1006724826083

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