title: Insulin-like growth factor binding protein 7 modulates estrogen-induced trophoblast proliferation and invasion in HTR-8 and JEG-3 cells.
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.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology of Chinese Academy of Sciences, Chaoyang District, Beijing, People's Republic of China.
authors.forename: Zhen-Kun
authors.initials: ZK
authors.lastname: Liu
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Liu
authors.forename: Wen-Ning
authors.initials: WN
authors.lastname: Fang
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Wang
authors.forename: Jing-Pian
authors.initials: JP
authors.lastname: Peng
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D000077267:Fulvestrant; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000276:immunology; D014327:Trophoblasts / Q000166:cytology*
chemical_list: D057134:Antibodies, Neutralizing; D004967:Estrogens; D018969:Insulin-Like Growth Factor Binding Proteins; D018809:Proliferating Cell Nuclear Antigen; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C102529:insulin-like growth factor binding protein-related protein 1; D000077267:Fulvestrant; D004958:Estradiol; D007371:Interferon-gamma; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9