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Abstract: Objective: Fibroblast growth factors (FGF) axis, and in particular FGF2 axis, is an important mitogenic stimulus in endometrial carcinogenesis. hSef is a key inhibitory regulator of FGF signaling and aberrant hSef expression is reported to be present in various human carcinomas. The objective of this study was to investigate the role of hSef in the growth and proliferation of endometrial adenocarcinoma cells and to explore the mechanism that may be involved. Methods: Using western blot analysis, we determined the expression of hSef in Ishikawa cells under different conditions. Using luciferase reporter assays and western blot analysis, we detected the effect of hSef on MAPK/ERK-mediated FGF2 signaling. Using MTT, cell counting and colony formation assays, we analyzed the growth and proliferation of Ishikawa cells under different conditions. Results: We found that the hSef expression was positively regulated by FGF2-induced MAPK/ERK signaling and inversely, hSef expression efficiently inhibited the activity of FGF2-induced MAPK/ERK signaling, indicating the presence of hSef-mediated negative feedback mechanism for FGF signaling in endometrial cancer cells. In addition, we found that MAPK/ERK signaling was essential for the growth and proliferation of endometrial cancer cells in vitro, and hSef expression significantly reduced the cell proliferation. Conclusions: hSef expression can inhibit the growth and proliferation of endometrial cancer cells via acting on the FGF2/MAPK/ERK signaling. [Copyright &y& Elsevier]