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Growth-suppressing function of glypican-3 (GPC3) via insulin like growth factor II (IGF-II) signaling pathway in ovarian clear cell carcinoma cells
- Source :
- Gynecologic Oncology. 119:332-336
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
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 100ng/ml IGF-II. Furthermore, these effects were significantly attenuated by pretreatment with 1μM 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.
- Subjects :
- Cell Growth Processes
Biology
Transfection
Glypican 3
Wortmannin
Phosphatidylinositol 3-Kinases
chemistry.chemical_compound
Glypicans
Insulin-Like Growth Factor II
Cell Line, Tumor
Humans
RNA, Small Interfering
Protein kinase B
PI3K/AKT/mTOR pathway
Ovarian Neoplasms
Cell growth
Obstetrics and Gynecology
Immunohistochemistry
Oncology
chemistry
Cell culture
Gene Knockdown Techniques
Clear cell carcinoma
Neoplastic Stem Cells
Cancer research
Female
Proto-Oncogene Proteins c-akt
Adenocarcinoma, Clear Cell
Signal Transduction
Subjects
Details
- ISSN :
- 00908258
- Volume :
- 119
- Database :
- OpenAIRE
- Journal :
- Gynecologic Oncology
- Accession number :
- edsair.doi.dedup.....440f5ae21a1e08e6231c8dfeb3380094