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Dual-specificity phosphatase 6 (Dusp6), a negative regulator of FGF2/ERK1/2 signaling, enhances 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell.

Abstract
Dual-specificity phosphatase 6 (Dusp6) is a negative feedback mechanism of fibroblast growth factors (FGFs)/mitogen-activated protein kinase (MAPK)/ERK1/2 signaling. The aim of this study was to explore the expression of Dusp6 in human endometrial adenocarcinomas and the role of Dusp6 expression in the growth regulation of endometrial adenocarcinoma cell. We found that Dusp6 was over-expressed in human endometrial adenocarcinomas. In Ishikawa cells, plasmid-driven Dusp6 expression efficiently blocked the activity of FGF2-induced MAPK/ERK1/2 signaling. Unexpectedly, Dusp6 expression significantly enhanced the growth of Ishikawa cells. In Dusp6 forced-expression cells, 17β-estradiol stimulation increased the cell growth by all most threefolds. In addition, progesterone treatment reduced the cell growth to about half both in Ishikawa cells with and without forced-Dusp6-expression. Dusp6 over-expression is involved in the pathogenesis and development of human endometrial adenocarcinomas. Dusp6 functions as a negative regulator of FGF2/ERK1/2 signaling but enhances the growth and 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell.
AuthorsHui Zhang, Qiufen Guo, Chong Wang, Lei Yan, Yibing Fu, Mingjun Fan, Xingbo Zhao, Mingjiang Li
JournalMolecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 376 Issue 1-2 Pg. 60-9 (Aug 25 2013) ISSN: 1872-8057 [Electronic] Ireland
PMID23419500 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013. Published by Elsevier Ireland Ltd.
Chemical References
  • Fibroblast Growth Factor 2
  • Progesterone
  • Estradiol
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • DUSP6 protein, human
  • Dual Specificity Phosphatase 6
Topics
  • Adenocarcinoma (genetics, metabolism, pathology)
  • Adult
  • Aged, 80 and over
  • Case-Control Studies
  • Cell Line, Tumor
  • Dual Specificity Phosphatase 6 (genetics, metabolism)
  • Endometrial Neoplasms (genetics, metabolism, pathology)
  • Estradiol (pharmacology)
  • Female
  • Fibroblast Growth Factor 2 (genetics, metabolism)
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Humans
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 (genetics, metabolism)
  • Mitogen-Activated Protein Kinase 3 (genetics, metabolism)
  • Progesterone (pharmacology)
  • Signal Transduction (drug effects)

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