The mechanism and significance of synergistic induction of the expression of plasminogen activator inhibitor-1 by glucocorticoid and transforming growth factor beta in human ovarian cancer cells

被引：7

作者：

Pan, Xiao-yu ^{[1
]}

Wang, Yan ^{[2
]}

Su, Jie ^{[2
]}

Huang, Gao-xiang ^{[2
]}

Cao, Dong-mei ^{[2
]}

Qu, Shen ^{[1
]}

Lu, Jian ^{[2
]}

机构：

[1] Tongji Univ, Shanghai Peoples Hosp 10, Dept Endocrinol, Shanghai 200072, Peoples R China

[2] Second Mil Med Univ, Dept Pathophysiol, Shanghai 200433, Peoples R China

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2015年 / 407卷 / 0C期

基金：

中国国家自然科学基金;

关键词：

Plasminogen activator inhibitor-1; Dexamethasone; Transforming growth factor beta; Phosphorylation; Ovarian cancer; HUMAN-LUNG FIBROBLASTS; TGF-BETA; RECEPTOR PHOSPHORYLATION; SIGNALING PATHWAYS; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVITY; LYMPHOID-CELLS; CROSS-TALK; SMAD; TYPE-1;

D O I：

10.1016/j.mce.2015.03.005

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

引用

页码：37 / 45

页数：9

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