C-Fos-Regulated Matrix Metalloproteinase-9 Expression is Involved in 17β-Estradiol-Promoted Invasion of Human Endometrial Stromal Cell.

Abstract

Endometriosis is a frequent gynecological disease associated with severe pain and infertility. Although its dependency on estrogen is well recognized, the molecular mechanism along the estrogenic pathway has not been fully understood. This study investigates the effect of 17β-estradiol (E2) on human endometrial stromal cell (HESC) invasion and the role of c-fos and matrix metalloproteinase-9 (MMP-9) in mediating the biological function of 17β-E2. It is found that 17β-E2 promotes not only HESC invasion, but also c-fos and MMP-9 expression in HESC. Further experiments demonstrate that the estrogen receptor inhibitor ICI 182780 and siRNA-mediated c-fos or MMP-9 knockdown are able to block the effect of 17β-E2 on HESC invasion. Moreover, siRNA-mediated c-fos knockdown suppresses the effect of 17β-E2 on MMP-9 expression. Our results indicate that 17β-E2-induced HESC invasion is dependent on c-fos-mediated MMP-9 expression. These findings facilitate our understanding on the pathogenesis of endometriosis and may provide data potentially useful for the development of new treatment modalities for better management of endometriosis.