Citation

  • Authors: Pan, X. Y., Wang, Y., Su, J., Huang, G. X., Cao, D. M., Qu, S., Lu, J.
  • Year: 2015
  • Journal: Mol Cell Endocrinol 407 37-45
  • Applications: in vitro / siRNA / INTERFERin
  • Cell types:
    1. Name: HO-8910
      Description: Human epithelial ovarian cancer cell line.
    2. Name: SK-OV-3
      Description: Human ovary carcinoma cells
      Known as: SKOV3, SKOV-3

Method

10 nM of siRNA.

Abstract

Plasminogen activator inhibitor-1 (PAI-1) plays a key role in tissue remodeling and tumor development by suppression of plasminogen activator function. Glucocorticoids (GCs) and transforming growth factor beta (TGF-beta) signal pathways cross-talk to regulate gene expression, but the mechanism is poorly understood. Here we investigated the mechanism and significance of co-regulation of PAI-1 by TGF-beta and dexamethasone (DEX), a synthetic glucocorticoid in ovarian cancer cells. We found that TGF-beta and DEX showed rapidly synergistic induction of PAI-1 expression, which contributed to the early pro-adhesion effects. The synergistic induction effect was accomplished by several signal pathways, including GC receptor (GR) pathway and TGF-beta-activated p38MAPK, ERK and Smad3 pathways. TGF-beta-activated p38MAPK and ERK pathways cross-talked with GR pathway to augment the expression of PAI-1 through enhancing DEX-induced GR phosphorylation at Ser211 in ovarian cancer cells. These findings reveal possible novel mechanisms by which TGF-beta pathways cooperatively cross-talk with GR pathway to regulate gene expression.

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