Document Detail


Growth-suppressing function of glypican-3 (GPC3) via insulin like growth factor II (IGF-II) signaling pathway in ovarian clear cell carcinoma cells.
MedLine Citation:
PMID:  20701957     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Maiko Sakurai; Kiyosumi Shibata; Tomokazu Umezu; Hiroaki Kajiyama; Eiko Yamamoto; Kazuhiko Ino; Akihiro Nawa; Fumitaka Kikkawa
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Publication Detail:
Type:  Journal Article     Date:  2010-08-10
Journal Detail:
Title:  Gynecologic oncology     Volume:  119     ISSN:  1095-6859     ISO Abbreviation:  Gynecol. Oncol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-11     Completed Date:  2010-10-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0365304     Medline TA:  Gynecol Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  332-6     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / metabolism
Adenocarcinoma, Clear Cell / genetics,  metabolism*,  pathology*
Cell Growth Processes / physiology
Cell Line, Tumor
Female
Gene Knockdown Techniques
Glypicans / biosynthesis,  genetics,  metabolism*
Humans
Immunohistochemistry
Insulin-Like Growth Factor II / metabolism*
Neoplastic Stem Cells / metabolism,  pathology
Ovarian Neoplasms / genetics,  metabolism*,  pathology*
Proto-Oncogene Proteins c-akt / metabolism
RNA, Small Interfering / genetics
Signal Transduction
Transfection
Chemical
Reg. No./Substance:
0/GPC3 protein, human; 0/Glypicans; 0/RNA, Small Interfering; 67763-97-7/Insulin-Like Growth Factor II; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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