title: Placenta growth factor induces invasion and activates p70 during rapamycin treatment in trophoblast cells.
abstract: OBJECTIVE
  Aberrant trophoblast invasion has been associated with human intrauterine growth restriction (IUGR) and preeclampsia (PE). Our objective was to determine placenta growth factor (PlGF)-mediated regulation of cell invasion in trophoblast cells with reduced mammalian target of Rapamycin (mTOR) signaling.
  
  
  METHODS
  First trimester SW 71 trophoblast cells were subjected to invasion assays with the following conditions: 10% FBS, 10% FBS with Rapamycin, and 10% FBS with Rapamycin and PlGF. mTOR siRNA was also done in these cells. Western blots were performed on cell lysates with antibodies against phospho- and total mTOR, 70-kDa ribosomal protein kinase I (p70), 4EBP1, extracellular regulated kinase (ERK), and phosphatidylinositol-3 kinase (AKT).
  
  
  RESULTS
  Compared to controls, trophoblast cells showed: (i) a 33% decrease in invasion following Rapamycin treatment, (ii) protection from decreased invasion following Rapamycin and PlGF treatment, (iii) a 31% decrease in mTOR phosphorylation with Rapamycin, (iv) increased phosphorylation of p70 (43%) with Rapamycin and PlGF, and (v) a 76% decrease in invasion following mTOR depletion.
  
  
  CONCLUSIONS
  We conclude that first trimester trophoblast invasion is functionally decreased when phosphorylation of mTOR is prevented and this decrease is recovered with the addition of PlGF. Mechanistically, this recovery involves the phosphorylation of p70 independent of mTOR.
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Knuth
authors.forename: Lawrence
authors.initials: L
authors.lastname: Liu
authors.forename: Halden
authors.initials: H
authors.lastname: Nielsen
authors.forename: Daniel
authors.initials: D
authors.lastname: Merril
authors.forename: Donald S
authors.initials: DS
authors.lastname: Torry
authors.forename: Juan A
authors.initials: JA
authors.lastname: Arroyo
mesh_terms: D002460:Cell Line; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins; D017027:Protein Tyrosine Phosphatases; D051057:Proto-Oncogene Proteins c-akt; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C000608036:PGF protein, human; C546842:MTOR protein, human; C489397:UBASH3B protein, human
keywords: Mammalian target of Rapamycin; placenta; placenta growth factor; trophoblast invasion