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-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.


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.


CONCLUSIONS
This study directly implicates ErbB receptors in the activation of NF-kappaB in PC-3 prostate cancer cells.
Le Page
Cécile
C
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM) and Institut du Cancer de Montréal, Quebec, Canada.
Koumakpayi
Ismael Hervé
IH
Lessard
Laurent
L
Mes-Masson
Anne-Marie
AM
Saad
Fred
F
D066246:ErbB Receptors / Q000502:physiology*; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis* / Q000502:physiology; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology*; D014407:Tumor Cells, Cultured
D066246:ErbB Receptors; D016328:NF-kappa B; D018719:Erb-b2 Receptor Tyrosine Kinases