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‐κB) in prostate cancer cells, although the mechanism by which these receptors activate NF‐κB 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‐κB through two different mechanisms. EGFR activates NF‐κB through the PI3K/Akt pathway that leads to the phosphorylation of IκBα on serines 32 and 36, thereby promoting the nuclear translocation of the p65 subunit. In contrast, Her‐2 activates NF‐κB through Casein Kinase II (CK‐2) activation independently of IκBα phosphorylation on serines 32 and 36. CONCLUSIONS Our study not only directly clarifies the signaling pathways involved in NF‐κB activation in prostate cancer cell lines and but also provides a framework for further studies in the clinical characterization and management of prostate cancer. Prostate. © 2005 Wiley‐Liss, Inc.