Journal Article

Downregulation of HER2 by RIG1 involves the PI3K/Akt pathway in ovarian cancer cells

Chien-Chih Ou, Shih-Chung Hsu, Yin-Hui Hsieh, Wan-Ling Tsou, Tzu-Chao Chuang, Jah-Yao Liu and Ming-Ching Kao

in Carcinogenesis

Volume 29, issue 2, pages 299-306
Published in print February 2008 | ISSN: 0143-3334
Published online January 2008 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm263
Downregulation of HER2 by RIG1 involves the PI3K/Akt pathway in ovarian cancer cells

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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.

Journal Article.  5153 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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