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Nur77 has a critical role in ovarian cancer progression through the regulation of the TGF-β signaling pathway

 
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Pathophysiology of Cell Injury Journal  Volume 3, Issue 2, pages 60-72 December 2014

Alex J Danielson; Neil K Barnes; Stephen T Gurantz; Borg A Dunne; Leo Chung; Jan H Turner; Van G Porter

Abstract

Ovarian cancer is characterized by malignant transformation of ovarian epithelial, stromal, or germ line cells, the TGF-β pathway acts as an oncogenic factor and is considered to be a therapeutic target. We are hypothesis that Nur77 induced TGF-β signaling in ovarian cancer cell.  We investigated the activity of Nur77 and TGF-b in human ovarian cancer and both in vitro and in vivo by used cell lines inoculated in nude mice with back ground Nur77-/- and C57BL/6. Human ovarian cancer cell over-expressed Nur77 in all high-grade serous carcinoma and less extent to other types of ovarian cancer, and potently induced TGF-b expression were detected by immunoblot staining.Whereas loss of Nur77 inhibits TGF-β-expression in Nur77-/- nude mice. Importantly, Nur77 KO reduced the size of ovarian cancer tumor in mice. Our results show that Nur77 as an important determinant for hyperactivation of pro-oncogenic TGF-β signaling in ovarian cancer, and suggest a target for Nur77, which may be useful for future clinical applications.

Keywords: Nur77; TGF-β; Ovarian cancer; Tumor xenografts

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