title: AP-1 Transcription Factors c-FOS and c-JUN Mediate GnRH-Induced Cadherin-11 Expression and Trophoblast Cell Invasion.
abstract: GnRH is expressed in first-trimester human placenta and increases cell invasion in extravillous cytotrophoblasts (EVTs). Invasive phenotypes have been reported to be regulated by transcription factor activator protein 1 (AP-1) and mesenchymal cadherin-11. The aim of our study was to investigate the roles of AP-1 components (c-FOS/c-JUN) and cadherin-11 in GnRH-induced cell invasion in human EVT cells. Phosphorylated c-FOS and phosphorylated c-JUN were detected in the cell column regions of human first-trimester placental villi by immunohistochemistry. GnRH treatment increased c-FOS, c-JUN, and cadherin-11 mRNA and protein levels in immortalized EVT (HTR-8/SVneo) cells. Moreover, GnRH treatment induced c-FOS and c-JUN protein phosphorylation and nuclear accumulation. Pretreatment with antide, a GnRH antagonist, attenuated GnRH-induced cadherin-11 expression. Importantly, basal and GnRH-induced cadherin-11 expression and cell invasion were reduced by small interfering RNA-mediated knockdown of c-FOS, c-JUN, and cadherin-11 in HTR-8/SVneo cells. Our results suggest that GnRH induces the expression and phosphorylation of the AP-1 transcription factors c-FOS and c-JUN in trophoblast cells, which contributes to GnRH-induced elevation of cadherin-11 expression and cell invasion.
authors: Department of Obstetrics and Gynaecology (B.P., H.Z., C.K., P.C.K.L.), Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4; and State Key Laboratory of Reproductive Biology (L.M., Y.W.), Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
authors: Bo
authors: B
authors: Peng
authors: Hua
authors: H
authors: Zhu
authors: Liyang
authors: L
authors: Ma
authors: Yan-Ling
authors: YL
authors: Wang
authors: Christian
authors: C
authors: Klausen
authors: Peter C K
authors: PC
authors: Leung
mesh_terms: D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D008856:Microscopy, Fluorescence; D011247:Pregnancy; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology*
chemical_list: D015820:Cadherins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; C086960:osteoblast cadherin; D007987:Gonadotropin-Releasing Hormone