title: OPN induces FoxM1 expression and localization through ERK 1/2, AKT, and p38 signaling pathway in HEC-1A cells.
abstract: Mammalian embryo implantation is an extremely complex process and requires endometrial receptivity. In order to establish this receptivity, sequential proliferation and differentiation during the menstrual cycle is necessary. Forkhead box M1 (FoxM1) is described as a major oncogenic transcription factor in tumor initiation, promotion and progression. According to these functions, we believe that FoxM1 should also play an essential role in embryo implantation. Osteopontin (OPN), an adhesion molecule, has been studied extensively in reproduction. In this study, we observed the expression and distribution of FoxM1 during the proliferative-phase and secretory-phase human endometrium and the pre-implantation mouse uterus firstly. Then we observed the relationship between OPN and FoxM1. Our results showed that FoxM1 was mainly distributed in glandular epithelium. OPN increased the expression of FoxM1 in the human uterine epithelial cell line HEC-1A cells in a time- and concentration-dependent manner. OPN regulates FoxM1 to influence HEC-1A cell proliferation through extracellular regulated protein kinases (ERK 1/2), protein kinase B (PKB, AKT), and the p38 mitogen activated protein kinases (p38MAPK, p38) signaling pathway. Inhibition of ERK 1/2, AKT and p38 suppressed OPN-induced FoxM1 expression and location. Our data indicate that FoxM1 might be regulated by OPN to influence endometrial proliferation to establish endometrial receptivity.
authors.affiliation: Department of Biochemistry and Molecular, Dalian Medical University, Dalian 116044, China. yunpeng_xie1986@163.com.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Biochemistry and Molecular, Dalian Medical University, Dalian 116044, China. yinghua_li1989@163.com.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular, Dalian Medical University, Dalian 116044, China. yingkong@dlmedu.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Kong
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D053495:Osteopontin / Q000378:metabolism* / Q000494:pharmacology; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D011994:Recombinant Proteins; D053495:Osteopontin; D051057:Proto-Oncogene Proteins c-akt