Independent role of phosphoinositol-3-kinase (PI3K) and casein kinase II (CK-2) in EGFR and Her-2-mediated constitutive NF-kappaB activation in prostate cancer cells
Copyright policy )Independent role of phosphoinositol-3-kinase (PI3K) and casein kinase II (CK-2) in EGFR and Her-2-mediated constitutive NF-kappaB activation in prostate cancer cells
Recent research has highlighted the potential role of EGFR and Her-2 in the constitutive activation of NF-kappaB (NF-kappaB) in prostate cancer cells, although the mechanism by which these receptors activate NF-kappaB in these cells remains unclear.Using pharmacological and genetic approaches we show that in PC-3 cells, EGFR and Her-2 are involved in the constitutive activation of NF-kappaB through two different mechanisms. EGFR activates NF-kappaB through the PI3K/Akt pathway that leads to the phosphorylation of IkappaBalpha on serines 32 and 36, thereby promoting the nuclear translocation of the p65 subunit. In contrast, Her-2 activates NF-kappaB through Casein Kinase II (CK-2) activation independently of IkappaBalpha phosphorylation on serines 32 and 36.Our study not only directly clarifies the signaling pathways involved in NF-kappaB activation in prostate cancer cell lines and but also provides a framework for further studies in the clinical characterization and management of prostate cancer.
- Fondation du CHUM Canada
- University of Montreal Canada
Male, Receptor, ErbB-2, Morpholines, Blotting, Western, NF-kappa B, Prostatic Neoplasms, Electrophoretic Mobility Shift Assay, Enzyme Activation, ErbB Receptors, Phosphatidylinositol 3-Kinases, NF-KappaB Inhibitor alpha, Chromones, Cell Line, Tumor, Humans, I-kappa B Proteins, Enzyme Inhibitors, Phosphorylation, Casein Kinase II, Phosphoinositide-3 Kinase Inhibitors, Signal Transduction
Male, Receptor, ErbB-2, Morpholines, Blotting, Western, NF-kappa B, Prostatic Neoplasms, Electrophoretic Mobility Shift Assay, Enzyme Activation, ErbB Receptors, Phosphatidylinositol 3-Kinases, NF-KappaB Inhibitor alpha, Chromones, Cell Line, Tumor, Humans, I-kappa B Proteins, Enzyme Inhibitors, Phosphorylation, Casein Kinase II, Phosphoinositide-3 Kinase Inhibitors, Signal Transduction
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