Expression of c-Ets1 protein in normal human placenta.

Background: The proto-oncogene product c-Ets1 is a transcriptional factor that controls the expression of a number of genes involved in extracellular matrix remodeling such as stromelysin-1 (matrix metalloproteinase-3; MMP-3), collagenase-1, and urokinase-type plasminogen activator (u-PA). To elucidate the involvement of c-Ets1 in the invasive pathway of the trophoblasts, we analyzed c-Ets1 protein expression in placentas by fluorescent immunohistochemistry and Western blot analysis. Methods: We analyzed serial frozen sections for c-Ets1 protein expression of the chorionic villi and cell column in the first trimester and the basal plate of placenta and amniotic membranes in the third trimester by fluorescent immunohistochemistry. Moreover, we examined the expression of c-Ets1 in the first and the third trimester by Western blot analysis. Results: In the first trimester, c-Ets1 was strongly expressed in the cytoplasm of cytotrophoblasts. Moreover, the cell column that invaded the endometrium had the strongest expression of c-Ets1. In the third trimester, c-Ets1 was detected in both cytoplasm and nucleus of the invading trophoblasts in the basal plate. Furthermore, c-Ets1 was expressed in both cytoplasm and nucleus of the trophoblasts in amniotic membrane. Western blotting revealed that c-Ets1 expressions in the first trimester were stronger than those in the third trimester. Conclusion: Our results demonstrate that c-Ets1 expression in normal human placenta correlates to the invasive behavior of the trophoblasts, probably by activating the transcription of matrix-degrading MMPs, including MMP-3, collagenase-1, and u-PA.