Role of TGF-β1-activated p38 MAPK in up-regulation of PAI-1 expres-sion by TGF-β1 in human ovarian cancer cells / 中国病理生理杂志

ABSTRACT

AIM: To investigate the relationship between up-regulation of plasminogen activator inhibitor-1 (PAI-1) expression and activation of p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated kinase ( ERK) pathways by TGF-β1 in human ovarian cancer cells .METHODS: PAI-1 expression in human ovarian cancer cells treated with TGF-β1 (10 μg/L)was assayed by real-time PCR and Western blotting.The activation of p38 MAPK and ERK was determined by Western blotting using phosphorylated p 38 MAPK and phosphorylated ERK antibodies . Specific p38 MAPK inhibitor (SB203580) or ERK inhibitor (PD98059) was used to inhibit their activation .RESULTS:TGF-β1 up-regulated the expression of PAI-1, and activated p38 MAPK and ERK pathways in the ovarian cancer cells .In-hibition of p38 MAPK activation by SB203580 resulted in significant inhibition of the mRNA expression of PAI-1 induced by TGF-β1.However, inhibition of ERK activation did not significantly alter TGF-β1-induced increase in PAI-1 mRNA level.CONCLUSION: TGF-β1-activated p38 MAPK pathway contributes to the up-regulation of PAI-1 expression by TGF-β1 in ovarian cancer cells .