EGF rescues LNCaP cells from LY294002-induced apoptosis through ERK1/2 activation mediated by an increase of ERBB2

M. ALICIA CORTÉS

Istambul

Congreso; 31st FEBS congress; 2006

FEBS

INTRODUCTION: The PI3K/Akt pathway is constitutively active in LNCaP cells due to a mutation in the PTEN, a negative regulator of this pathway. In vivo, the PTEN loss is correlated with a substantial increase in Akt activity which is an excellent predictor of poor clinical outcome in prostate cancer. The importance of this pathway for cell survival is obvious since treatment with the PI3K inhibitor LY294002 (LY) leads to apoptosis. EGF antagonizes this apoptotic effect, although the molecular mechanisms involved are unknown. The goal of this study was to identify the PI3K-independent cell survival pathway activated by EGF in LNCaP cells. CONCLUSIONS:  In the absence of PI3K/Akt, EGF increases ErbB2 levels and promotes long-term activation of ErK1/2. The increase of ErbB2 levels induce a higher ErbB2 phosphorylation through increase EGFR-ErbB2 heterodimer formation. EGF rescues LNCaP cells from apoptosis induced by the absence of PI3K/Akt through EGF-induced ERK1/2 sustained activation by an increase of ErbB2.