EGFR and her-2 regulate the constitutive activation of NF-KappaB in PC-3 prostate cancer cells

BACKGROUND. The mechanism through which NF-kappaB (NF-kappa B) is constitutively activated in prostate cancer cells remains unclear. We investigated whether members of the ErbB family of epidermal growth factor receptors (EGFR) are involved in the constitutive activation of NF-kappa B in prostate cancer cell lines. METHODS AND RESULTS. EGFR, Her-2, and ErbB3 are expressed and constitutively activated in PC-3, DU145, and LNCaP prostate cancer cells lines. Using several pharmacological ErbB inhibitors, we demonstrate that EGFR and Her-2 are involved in the constitutive activation of NF-kappa B in PC-3 cells through two different mechanisms. EGFR activates NF-kappa B through the phosphorylation of I kappa B alpha on serines 32/36 thereby influencing the nuclear translocation of the p65 subunit. In contrast, Her-2 activates NF-kappa B independently of I kappa B alpha phosphorylation on serines 32/36. CONCLUSION. This study directly implicates ErbB receptors in the activation of NF-kappa B in PC-3 prostate cancer cells.