title: c-Rel Promotes Invasion of Choriocarcinoma Cells via PI3K/AKT Signaling.
abstract: OBJECTIVE
  Choriocarcinoma is the most common epithelial cancer among gestational trophoblastic diseases (GTDs); the mechanism of trophoblastic carcinogenesis is unknown. This study aimed to examine the expression of NF-κB family proteins in GTDs and placental tissues as well as the roles of c-Rel in choriocarcinoma.
  
  
  METHODS
  We examined the expression of NF-κB family proteins in normal placenta and hydatidiform mole tissues as well as extravillous trophoblast (EVT) and choriocarcinoma cell lines by Western blot and immunohistochemistry. Immunoprecipitation was performed to determine which proteins can bind with c-Rel in choriocarcinoma cells. To investigate the roles of c-Rel in choriocarcinoma, we examined the effects of c-Rel knockdown and overexpression on cell proliferation, migration, and invasion using small interfering RNAs and gene activation plasmid.
  
  
  RESULTS
  The expression of c-Rel was strong in choriocarcinoma and EVTs, but very weak in villi of normal placenta and hydatidiform mole. Immunoprecipitation suggested that c-Rel heterodimerizes with p65 in choriocarcinoma. c-Rel knockdown reduced invasion, migration, and AKT phosphorylation in choriocarcinoma cells. c-Rel overexpression in choriocarcinoma increased migratory and invasive abilities, and the effect on invasion was inhibited by a PI3K inhibitor.
  
  
  CONCLUSIONS
  These findings suggest that c-Rel might play a role in promoting the invasion of choriocarcinoma cells through PI3K/AKT signaling.
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sekiya
authors.forename: Eiko
authors.initials: E
authors.lastname: Yamamoto
authors.forename: Kaoru
authors.initials: K
authors.lastname: Niimi
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Nishino
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kotani
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kajiyama
authors.forename: Kiyosumi
authors.initials: K
authors.lastname: Shibata
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kikkawa
mesh_terms: D002460:Cell Line; D002822:Choriocarcinoma / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006828:Hydatidiform Mole / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism*; D015398:Signal Transduction; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D016328:NF-kappa B; D020569:Proto-Oncogene Proteins c-rel; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Choriocarcinoma; Invasion; Migration; c-Rel; p65