title: MUC1 expression is elevated in severe preeclamptic placentas and suppresses trophoblast cell invasion via β1-integrin signaling.
abstract: BACKGROUND
  Preeclampsia is a pregnancy-specific disorder that features insufficient extravillous trophoblast (EVT) invasion. We have previously shown that MUC1 expression in human placenta increases with gestational age and inhibits choriocarcinoma cell invasion.
  
  
  OBJECTIVE
  Here, we studied whether MUC1 expression in preeclamptic placentas is dysregulated and the mechanism of EVT invasion regulated by MUC1.
  
  
  METHODS
  MUC1 expression in severe preeclamptic placentas and gestational age-matched control placentas was analyzed by real-time RT-PCR, Western blot analysis, and immunohistochemistry. The effects of MUC1 expression on cell-matrix adhesion, invasion, and cell signaling were studied in HTR8/SVneo EVT cells.
  
  
  RESULTS
  We found that MUC1 mRNA and MUC1 protein were significantly up-regulated in severe preeclamptic placentas when compared with the gestational age-matched control placentas. Immunohistochemical analyses showed increased expression of MUC1 in the syncytiotrophoblast and EVT of severe preeclamptic placentas. In addition, MUC1 overexpression suppressed cell-matrix adhesion and invasion of EVT cells. Importantly, our data showed that MUC1 overexpression inhibited β1-integrin activity and phosphorylation of focal adhesion kinase, whereas the surface expression of β1-integrin was not significantly changed.
  
  
  CONCLUSIONS
  Our findings suggest that MUC1 is overexpressed in severe preeclamptic placentas and that MUC1 overexpression suppresses EVT invasion mainly via modulating β1-integrin signaling.
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei 100, Taiwan.
authors.forename: Ming-Kwang
authors.initials: MK
authors.lastname: Shyu
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Chen
authors.forename: Neng-Yu
authors.initials: NY
authors.lastname: Lin
authors.forename: Wen-Chieh
authors.initials: WC
authors.lastname: Liao
authors.forename: Chi-Hau
authors.initials: CH
authors.lastname: Chen
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Lin
authors.forename: Hsiu-Chin
authors.initials: HC
authors.lastname: Huang
authors.forename: Jian-Jr
authors.initials: JJ
authors.lastname: Lee
authors.forename: Miao-Juei
authors.initials: MJ
authors.lastname: Huang
authors.forename: Guo-Fang
authors.initials: GF
authors.lastname: Tseng
authors.forename: Jin-Chung
authors.initials: JC
authors.lastname: Shih
authors.forename: Chien-Nan
authors.initials: CN
authors.lastname: Lee
authors.forename: Fon-Jou
authors.initials: FJ
authors.lastname: Hsieh
authors.forename: Min-Chuan
authors.initials: MC
authors.lastname: Huang
mesh_terms: D000328:Adult; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D019012:Integrin beta1; C060192:MUC1 protein, human; D018396:Mucin-1