Results
| PMID | 21984126 |
| Gene Name | DUSP2 |
| Condition | Endometriosis |
| Association |
Associated |
| Sex | Female |
| Associated genes | COX-2, MAPK, HIF-1?, DUSP2 |
| Other associated phenotypes |
Endometriosis |
|
J Pathol. 2011 Nov;225(3):390-400. doi: 10.1002/path.2963. Epub 2011 Aug 24. Wu, Meng-Hsing| Lin, Shih-Chieh| Hsiao, Kuei-Yang| Tsai, Shaw-Jenq Department of Obstetrics and Gynecology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China. Endometriosis is one of the most common gynaecological diseases that significantly reduces the life qualify of affected women and their families. Aberrant expression of cyclooxygenase-2 (COX-2), and thus over-production of prostaglandin E(2) (PGE(2) ) has been shown to play critical roles in the development of this disease. However, the mechanism responsible for COX-2 over-expression remains obscure. Here, we provide evidence for what we believe is a novel mechanism in regulating COX-2 expression in endometriotic stromal cells. Dual-specificity phosphatase-2 (DUSP2), a nuclear phosphatase that inactivates mitogen-activated protein kinase (MAPK), is markedly down-regulated in stromal cells of ectopic endometriotic tissues, which results in prolonged activation of extracellular signal-regulated kinase (ERK) and p38 MAPK and increased COX-2 expression. Expression of DUSP2 is inhibited by hypoxia inducible factor-1alpha (HIF-1alpha) at the transcriptional level. Treatment of normal endometrial stromal cells with hypoxia, or chemicals that cause HIF-1alpha accumulation, results in DUSP2 down-regulation, prolonged ERK phosphorylation and COX-2 over-expression. In contrast, forced expression of DUSP2 under hypoxia abolishes HIF-1alpha-induced ERK phosphorylation and COX-2 expression. Furthermore, suppression of DUSP2 by HIF-1alpha in eutopic endometrial stromal cells increases sensitivity of cox-2 gene to interleukin-1beta stimulation, a phenomenon resembling endometriotic stromal cell characteristics. Taken together, these data suggest that DUSP2 is an important molecule in endometrial physiology and that hypoxia-inhibited DUSP2 expression is a critical factor for the development of endometriosis. Mesh Terms: Cell Hypoxia/physiology| Cyclooxygenase 2/biosynthesis/genetics/*metabolism| DNA Methylation| Down-Regulation/physiology| Dual Specificity Phosphatase 2/antagonists & inhibitors/biosynthesis/genetics/*physiology| Endometriosis/*enzymology/pathology| |
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