Insulin-Like Growth Factor Binding Protein 7 Modulates Estrogen-Induced Trophoblast Proliferation and Invasion in HTR-8 and JEG-3 Cells |
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Authors: | Zhen-Kun Liu Hai-Yan Liu Wen-Ning Fang Ying Yang Hong-Mei Wang Jing-Pian Peng |
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Institution: | (1) State Key Laboratory of Reproductive Biology, Institute of Zoology of Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing, 100101, People’s Republic of China;(2) Graduate University of the Chinese Academy of Sciences, Beijing, 100080, China; |
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Abstract: | Previous research has reported that IGFBP7 functions as a tumor suppressor gene in different tumors, but its role in the trophoblast
has not been elucidated. In this research, we studied the regulation mechanism of IGFBP7 in trophoblast proliferation and
invasion in HTR-8 and JEG-3 cell lines. We found that IGFBP7 was abundantly expressed in normal human syncytiotrophoblast
tissue samples but that this was lacking in hydatidiform moles. The proliferation and invasion capacities of HTR-8 and JEG-3
cells were significantly inhibited by recombinant IGFBP7. Estrogen (E2) stimulated the expression of IGFBP7 at a concentration
of 5–10 ng/mL. This stimulation was inhibited by the estrogen receptor antagonist Fulvestrant (ICI182.780) and a TGFβ-neutralizing
antibody. In conclusion, our data reveals that estrogen stimulates the expression of IGFBP7 through estrogen receptors and
TGFβ. The expression of IGFBP7 could be stimulated by TGFβ in a dose-dependent manner and inhibited by IFNγ in HTR-8 and JEG-3
cells. IGFBP7 could also inhibit the phosphorylation of ERK and the expression of PCNA, MMP2 and MMP9 in HTR-8 and JEG-3 cells.
These findings suggest that IGFBP7 is a key regulator of E2-induced trophoblast proliferation and invasion. |
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