title: Growth-suppressing function of glypican-3 (GPC3) via insulin like growth factor II (IGF-II) signaling pathway in ovarian clear cell carcinoma cells.
abstract: OBJECTIVE
  Ovarian clear cell carcinoma (CCC) is well known to be highly resistant to platinum-based chemotherapy. Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is overexpressed in only CCC of epithelial ovarian carcinoma subtypes. The purpose of this study was to identify the role of GPC3 in ovarian CCC.
  
  
  METHODS
  To evaluate the function of GPC3 in ovarian CCC cells, we generated an ovarian cancer cell line, KOC7C cells stably transfected with plasmids encompassing shRNA targeting GPC3 (shGPC cells), and compared cell growth and the colony-forming ability to control shRNA-transfected cells (shCon cells).
  
  
  RESULTS
  We showed that shGPC3 cells significantly increased cell growth and the colony-forming potential compared with shCon cells in 1% serum containing medium with 100 ng/ml IGF-II. Furthermore, these effects were significantly attenuated by pretreatment with 1 μM wortmannin (an inhibitor of PI3K/Akt).
  
  
  CONCLUSIONS
  We have demonstrated for the first time the presence of elevated levels of GPC3 protein associated with cell growth inhibition in CCC cells. Our data suggest that GPC3 has the potential to become a novel therapeutic target for ovarian CCC patients.
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Sakurai
authors.forename: Kiyosumi
authors.initials: K
authors.lastname: Shibata
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Umezu
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kajiyama
authors.forename: Eiko
authors.initials: E
authors.lastname: Yamamoto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ino
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nawa
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kikkawa
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D055785:Gene Knockdown Techniques; D053673:Glypicans / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014162:Transfection
chemical_list: C105937:GPC3 protein, human; D053673:Glypicans; D034741:RNA, Small Interfering; D007335:Insulin-Like Growth Factor II; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt