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    Title: Downregulation of HER2 by RIG1 involves the PI3K/Akt pathway in ovarian cancer cells
    Authors: Ou, Chien-Chih;Hsu, Shih-Chung;Hsieh, Yin-Hui;Tsou, Wan-Ling;Chuang, Tzu-Chao;Liu, Jah-Yao;Kao, Ming-Ching
    Contributors: 淡江大學化學學系
    Date: 2008-02
    Issue Date: 2013-05-31 11:35:31 (UTC+8)
    Publisher: Oxford: Oxford University Press
    Abstract: Interferon-γ (IFN-γ) is known to downregulate HER2 oncoprotein (p185HER2 or briefly p185) in prostate cancer cells. We demonstrate that the IFN-γ-induced retinoid-inducible gene 1 (RIG1) acts as a transrepressor of p185. Furthermore, we exhibit that RIG1 downregulates the activated (phosphorylated) form of p185 and phosphoinositide-3 kinase (PI3K)/serine/threonine-specific protein kinase (Akt) and the mammalian target of rapamycin (mTOR), downstream substrates of HER2. We also elucidate that heregulin (HRG) specifically restores the activation of p185 and Akt after their activities are reduced by RIG1. Additionally, expression of vascular endothelial growth factor (VEGF) increases through the HER2- and Akt/mTOR-signaling pathways, indicating that VEGF is downregulated by RIG1 within the cell. These findings suggest that RIG1 plays a role in IFN-γ-mediated therapy by downregulating p185 and its downstream PI3K/Akt/mTOR/VEGF-signaling pathway. These results may provide a new therapeutic mechanism for the clinical use of IFN-γ and RIG1.
    Relation: Carcinogenesis 29(2), pp.299-306
    DOI: 10.1093/carcin/bgm263
    Appears in Collections:[化學學系暨研究所] 期刊論文

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