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-kappaB) in prostate cancer cells, although the mechanism by which these receptors activate NF-kappaB in these cells remains unclear.


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-kappaB through two different mechanisms. EGFR activates NF-kappaB through the PI3K/Akt pathway that leads to the phosphorylation of IkappaBalpha on serines 32 and 36, thereby promoting the nuclear translocation of the p65 subunit. In contrast, Her-2 activates NF-kappaB through Casein Kinase II (CK-2) activation independently of IkappaBalpha phosphorylation on serines 32 and 36.


CONCLUSIONS
Our study not only directly clarifies the signaling pathways involved in NF-kappaB activation in prostate cancer cell lines and but also provides a framework for further studies in the clinical characterization and management of prostate cancer.
Le Page
Cécile
C
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM), 1560 rue Sherbrooke est, Montréal, Québec, Canada.
Koumakpayi
Ismael Hervé
IH
Lessard
Laurent
L
Saad
Fred
F
Mes-Masson
Anne-Marie
AM
D015153:Blotting, Western; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D020032:Tyrphostins / Q000494:pharmacology
D047390:Casein Kinase II; D002867:Chromones; D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D020672:I-kappa B Proteins; D009025:Morpholines; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; D020032:Tyrphostins; C000606204:NFKBIA protein, human; C106250:6,7-dimethoxy-3-phenylquinoxaline; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one