Role of ErbB2 in the prostaglandin E₂-induced enhancement of the mitogenic response to epidermal growth factor in cultured hepatocytes

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• 作者：John Ø ; degå ; rd ; ^{john.odegard@medisin.uio.no} ; Monica Aasrum ; Ingun H. Tveteraas ; Suman P. Bharath ; Dagny Sandnes ; Thoralf Christoffersen
• 关键词：PGE2 ; prostaglandin E2 ; EGF ; epidermal growth factor ; EGFR ; epidermal growth factor receptor ; ERK ; extracellular signal-regulated kinase ; PI3K ; phosphoinositide 3-kinase ; GPCR ; G-protein-coupled receptor ; RT-PCR ; reverse transcription polymerase chain rea
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：4 May, 2012
• 卷：421
• 期：2
• 页码：255-260
• 文件大小：435 K

摘要

Prostaglandin E₂ (PGE₂) enhances the mitogenic response to epidermal growth factor (EGF) in hepatocytes, but the underlying mechanisms are not clear. We previously observed that PGE₂ upregulates EGF-induced signalling in the MEK/ERK and PI3K/Akt pathways in hepatocytes. Other investigations have indicated that ErbB2 enhances the mitogenic effect of EGF in these cells. In the present study we found that treatment with PGE₂ increased ErbB2 and decreased ErbB3 expression at both the mRNA and protein level in cultured rat hepatocytes. Silencing of the ErbB2 expression with specific siRNA blocked the stimulation by PGE₂ and EGF of cyclin D1 expression and DNA synthesis. Both EGF and PGE₂ increased the expression of ERK and Akt, but while the effect of EGF was inhibited by ErbB2-directed siRNA, this did not affect the PGE₂-induced upregulation of ERK and Akt. These data suggest that PGE₂ can enhance the mitogenic effect of EGF both by increasing ErbB2 expression and by ErbB2-independent mechanisms.