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  • Title: EGFR and Her-2 regulate the constitutive activation of NF-kappaB in PC-3 prostate cancer cells.
    Author: Le Page C, Koumakpayi IH, Lessard L, Mes-Masson AM, Saad F.
    Journal: Prostate; 2005 Oct 01; 65(2):130-40. PubMed ID: 15880609.
    Abstract:
    BACKGROUND: The mechanism through which NF-kappaB (NF-kappaB) 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-kappaB 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-kappaB in PC-3 cells through two different mechanisms. EGFR activates NF-kappaB through the phosphorylation of IkappaBalpha on serines 32/36 thereby influencing the nuclear translocation of the p65 subunit. In contrast, Her-2 activates NF-kappaB independently of IkappaBalpha phosphorylation on serines 32/36. CONCLUSION: This study directly implicates ErbB receptors in the activation of NF-kappaB in PC-3 prostate cancer cells.
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