Premium
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
Author(s) -
Le Page Cécile,
Koumakpayi Ismael Hervé,
Lessard Laurent,
Saad Fred,
MesMasson AnneMarie
Publication year - 2005
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20291
Subject(s) - prostate cancer , phosphorylation , cancer research , protein kinase b , kinase , pi3k/akt/mtor pathway , prostate , casein kinase 2 , signal transduction , nf κb , cancer , medicine , biology , chemistry , protein kinase a , microbiology and biotechnology , mitogen activated protein kinase kinase
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.