期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 407, 期 C, 页码 37-45出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2015.03.005
关键词
Plasminogen activator inhibitor-1; Dexamethasone; Transforming growth factor beta; Phosphorylation; Ovarian cancer
资金
- National Natural Science Foundation of China [31301164, 91029722]
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.
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