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RESEARCH ARTICLE Activation of the MEK–S6 Pathway in High-grade Ovarian Cancers Aviva P. Ventura, BS,* Sabarinath Radhakrishnan, MD,* Ann Green, BS,* Sunitha K. Rajaram, PhD,* April N. Allen, BS,* Kathy O’Briant, MS,* Miche`l Schummer, PhD,* Beth Karlan, MD,w Nicole Urban, ScD,* Muneesh Tewari, MD, PhD,zy Charles Drescher, MD,* and Beatrice S. Knudsen, MD, PhD*J in ascites may be less responsive to MEK inhibition. The Abstract: The primary objective of this study is to show the phosphorylation of S6 as a specific biomarker for either MEK activation and analyze the regulation of the MEK- S6 kinase or PI3-kinase pathway activation should be used with caution. pathway in high-grade ovarian cancer. Phospho-ERK (pERK), Key Words: ovarian cancer, pathway activation, MEK, AKT, S6 a direct substrate of MEK and 2 phosphorylation sites on the ribosomal protein, S6, Ser235/236, and Ser240/244, which are (Appl Immunohistochem Mol Morphol 2010;18:499–508) 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 varian cancer is one of the most lethal malignant (IHC). pERK, pS6, pAKT, and p4EBP1 were also measured Odiseases
Applied Immunohistochemistry & Molecular Morphology – Wolters Kluwer Health
Published: Dec 1, 2010
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