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Activation of the MEK-S6 pathway in high-grade ovarian cancers
- Source :
- Applied immunohistochemistrymolecular morphology : AIMM. 18(6)
- Publication Year :
- 2010
-
Abstract
- The primary objective of this study is to demonstrate the activation and analyze the regulation of the MEK- S6 kinase pathway in high-grade ovarian cancer. Phospho-ERK (pERK), a direct substrate of MEK and two phosphorylation sites on the ribosomal protein, S6, Ser235/236 and Ser240/244, which are both targeted by the MEK and PI3-kinase/AKT pathways, were analyzed in 13 cell lines, 28 primary cancers and 8 cases of cancer cells from ascites. In primary cancers, ERK and S6 phosphorylation was measured by immunohistochemistry (IHC). pERK, pS6, pAKT and p4EBP1 were also measured by Western blotting (WB). The regulation of S6 phosphorylation by the MEK and PI3-kinase pathways was determined in ovarian cancer cell lines. We observed frequent pERK expression in primary ovarian cancers (100 % by WB, 75% by IHC) but not in ovarian cancer cells from ascites (25% of cases by WB). The activation of the AKT pathway, measured by pAKT expression occurred in 7 cases of primary ovarian cancer by WB, but in none of the ascites samples. In ovarian cancer cell lines, the MEK pathway had a greater effect on S6 phosphorylation in cells without hyperactive AKT signaling. Our data suggest that MEK is a potential drug target in high-grade ovarian cancer, however cancer cells with hyperactive AKT and cancer cells in ascites may be less responsive to MEK inhibition. The phosphorylation of S6 as a specific biomarker for either MEK or PI3-kinase pathway activation should be used with caution.
- Subjects :
- MAPK/ERK pathway
endocrine system
Histology
Blotting, Western
Antineoplastic Agents
Biology
Article
Pathology and Forensic Medicine
Phosphatidylinositol 3-Kinases
Predictive Value of Tests
Cell Line, Tumor
medicine
Biomarkers, Tumor
Humans
Phosphorylation
Protein kinase B
Protein Kinase Inhibitors
PI3K/AKT/mTOR pathway
Phosphoinositide-3 Kinase Inhibitors
Ovarian Neoplasms
Kinase
Ribosomal Protein S6 Kinases
Ovary
Ascites
medicine.disease
MAP Kinase Kinase Kinases
Immunohistochemistry
Up-Regulation
Medical Laboratory Technology
Cancer cell
Cancer research
Female
Ovarian cancer
Proto-Oncogene Proteins c-akt
Signal Transduction
Subjects
Details
- ISSN :
- 15334058
- Volume :
- 18
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Applied immunohistochemistrymolecular morphology : AIMM
- Accession number :
- edsair.doi.dedup.....6fd83ff5cb2a2266432bbf30195bcb26