Transactivation of epidermal growth factor receptor by insulin-like growth factor 1 requires basal hydrogen peroxide |
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Authors: | Zhou Qiong Meng Dan Yan Bing Jiang Bing-Hua Fang Jing |
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Institution: | The Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Graduate School of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China. |
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Abstract: | Insulin-like growth factor (IGF-1) plays an important role in prostate cancer development. Recent studies suggest that IGF-1 has mitogenic action through epidermal growth factor receptor (EGFR). However, the mechanism remains largely unknown. Here, we demonstrated in prostate cancer DU145 cells that IGF-1 induced EGFR transactivation, leading to ERK activation. Matrix metalloproteinase-mediated shedding of heparin-binding EGF is involved in this process. Antioxidants and catalase inhibited IGF-1-stimulated EGFR phosphorylation, indicating that H(2)O(2) is required for EGFR activation. However, exogenous H(2)O(2) did not activate EGFR or IGF-1R in DU145 cells. IGF-1 did not induced production of H(2)O(2) in DU145 cells. Our results suggest that transactivation of EGFR by IGF-1 requires basal intracellular H(2)O(2) in DU145 cells. |
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Keywords: | EGF epithelial growth factor EGFR epithelial growth factor receptor HB-EGF heparin-binding EGF IGF-1 insulin-like growth factor IGF-1R IGF-1 receptor MAPK mitogen-activated protein kinase MMP matrix metalloproteinase NAC N-acetyl-cysteine PI3K phosphatidylinositol 3-kinase |
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