Downregulation of MMP-9 in ERK-mutated stable transfectants inhibits glioma invasion in vitro

Sajani S. Lakka, Sushma L. Jasti, Christopher Gondi, Douglas Boyd, Nirmala Chandrasekar, Dzung H. Dinh, William C. Olivero, Meena Gujrati, Jasti S. Rao

Research output: Contribution to journalArticle

Abstract

We previously showed that enhanced expression of MMP-9, an endopeptidase that digests basement-membrane type IV collagen, is related to tumor progression in vitro and in vivo; antisense-MMP-9 stably transfected clones were less invasive than untransfected parental cells and did not form tumors in nude mice. In this study, we examined the role of ERK-1 in the regulation of MMP-9 production and the invasive behavior of the human glioblastoma cell line SNB19, in which ERK1 is constitutively activated. SNB19 cells were stably transfected with mt-ERK, a vector encoding ERK-1 cDNA in which the conserved lysine at codon 71 was changed to arginine, thus impairing the catalytic efficiency of this enzyme. Gelatin zymography showed reduced levels of MMP-9 in the mt-ERK-transfected cell lines relative to those in vector-transfected and parental control cells. Reductions in MMP-9 protein mRNA levels were also detected in the mt-ERK-transfected cells by Western and Northern blotting. The mt-ERK-transfected cells were much less invasive than parental or vector control cells in a Matrigel invasion assay and in a spheroid coculture assay. Thus an ERK-dependent signaling pathway seems to regulate MMP-9 mediated glioma invasion in SNB19 cells; interfering with this pathway could be developed into a therapeutic approach, which aims at a reduction of cancer cell invasion.

Original languageEnglish (US)
Pages (from-to)5601-5608
Number of pages8
JournalOncogene
Volume21
Issue number36
DOIs
StatePublished - Jan 1 2002

Keywords

  • Extracellular signal regulated kinase
  • Gliomas
  • Invasion
  • MMP-9
  • Stable transfectants

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Lakka, S. S., Jasti, S. L., Gondi, C., Boyd, D., Chandrasekar, N., Dinh, D. H., Olivero, W. C., Gujrati, M., & Rao, J. S. (2002). Downregulation of MMP-9 in ERK-mutated stable transfectants inhibits glioma invasion in vitro. Oncogene, 21(36), 5601-5608. https://doi.org/10.1038/sj.onc.1205646