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Oncostatin M (OSM) Mediated Alterations in Matrix Metalloproteinase (MMP) ‐ 2 is Regulated by Specific Signal Transduction Pathways in H‐ras Transformed Cells
Author(s) -
Francis Eddie Joesph,
Hurta Robert A.R
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.607.6
Subject(s) - oncostatin m , signal transduction , microbiology and biotechnology , jak stat signaling pathway , biology , protein kinase b , protein kinase a , kinase , chemistry , cancer research , cytokine , interleukin 6 , tyrosine kinase , immunology
Oncostatin M (OSM) is a pleiotropic cytokine that has been shown to exert both stimulatory and inhibitory effects on tissue invasion in various cell lines. Tissue invasion is a key marker of metastasis and can be monitored by examining matrix metalloproteinase (MMP) activity. OSM has been shown to up‐regulate MMP‐2 protein expression and this regulation may involve the JAK‐STAT pathway for signal transduction. This present study elucidates a link between OSM, MMP‐2 protein expression and specific signal transduction pathways in NR3 cells (H‐ras transformed fibroblasts capable of benign tumor formation). The mitogen activated protein kinase (MAPK) pathway and the protein kinase C (PKC) pathway are involved in the OSM mediated alterations in MMP‐2 protein expression in NR3 cells. The P‐I‐3 kinase pathway and the AKT pathway are apparently not involved in this OSM mediated signaling mechanism in NR3 cells. Treatment of NR3 cells with OSM also resulted in the activation of specific members of the JAK‐STAT signal transduction pathway. Protein expression levels of JAK 1,2,3 and STAT 1,2,3,4 in NR3 cells were determined by Western blot analysis following treatment of NR3 cells with 50 ng/ml OSM for 24 hr. JAK1,2,3, STAT‐2, and STAT‐3 were involved in NR3's MMP‐2 response to OSM but STAT‐1 and STAT‐4 showed no apparent involvement in the signaling pathway [N.S.E.R.C. (R.A.R.H) and Canadian Cancer Society (P.E.I. Division)].