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

BACKGROUND: Recent research has highlighted the potential role of EGFR and Her-2 in the constitutive activation of NF-kappaB (NF-kappa B) in prostate cancer cells, although the mechanism by which these receptors activate NF-kappa B in these cells remains unclear. METHODS AND RESULTS: Using pharmacological and genetic approaches we show that in PC-3 cells, EGFR and Her-2 are involved in the constitutive activation of NF-kappa B through two different mechanisms. EGFR activates NF-kappa B through the PI3K/Akt pathway that leads to the phosphorylation of I kappa B alpha on serines 32 and 36, thereby promoting the nuclear translocation of the p65 subunit. In contrast, Her-2 activates NF-kappa B through Casein Kinase 11 (CK-2) activation independently of I kappa B alpha phosphorylation on serines 32 and 36. CONCLUSIONS: Our study of only directly clarifies the signaling pathways involved in NF kappa B activation in prostate cancer cell lines and but also provides a framework for further studies in the clinical characterization and management of prostate cancer.