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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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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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Acknowledgments

This study was supported by grants from the National Basic Research Program of China (No. 2011CB944402), the National Natural Science Foundation of China (No. 31171435), and the Knowledge Innovation Program in Chinese Academy of Sciences (KSCX2-EW-R-06).

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All authors declare that there are no conflicts of interest.

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  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

    Zhen-Kun Liu, Hai-Yan Liu, Wen-Ning Fang, Ying Yang, Hong-Mei Wang & Jing-Pian Peng

  2. Graduate University of the Chinese Academy of Sciences, Beijing, 100080, China

    Zhen-Kun Liu & Hai-Yan Liu

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Liu, ZK., Liu, HY., Fang, WN. et al. Insulin-Like Growth Factor Binding Protein 7 Modulates Estrogen-Induced Trophoblast Proliferation and Invasion in HTR-8 and JEG-3 Cells. Cell Biochem Biophys 63, 73–84 (2012). https://doi.org/10.1007/s12013-012-9342-5

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