Aromatic hydrocarbon receptor inhibits lysophosphatidic acid-induced vascular endothelial growth factor-A expression in PC-3 prostate cancer cells

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題名:	Aromatic hydrocarbon receptor inhibits lysophosphatidic acid-induced vascular endothelial growth factor-A expression in PC-3 prostate cancer cells
作者:	吳沛翊;Wu, Pei-Yi;Lin, Yueh-Chien;Lan, Shun-Yan;Huang, Yuan-Li;Lee, Hsinyu
貢獻者:	生醫理工學院生命科學系
關鍵詞:	60 APPLIED LIFE SCIENCES;AHR;ANGIOGENESIS;Angiogenesis Inducing Agents - antagonists & inhibitors;ANOXIA;AROMATICS;Aryl Hydrocarbon Receptor Nuclear Translocator - physiology;BIOLOGICAL FUNCTIONS;CARCINOGENESIS;Cell Line, Tumor;DIMERIZATION;DIOXIN;GROWTH FACTORS;HEK293 Cells;HIF-1;Humans;Hypoxia-Inducible Factor 1, alpha Subunit - metabolism;LIGANDS;LIPIDS;LPA;Lysophospholipids - antagonists & inhibitors;Lysophospholipids - physiology;Male;METASTASES;metastasis;neoplasm cells;Neoplasm Metastasis - pathology;Neoplasm Metastasis - prevention & control;NEOPLASMS;Neovascularization, Pathologic - pathology;Neovascularization, Pathologic - prevention & control;phosphatidylinositol 3-kinase;PROSTATE;prostatic neoplasms;Prostatic Neoplasms - metabolism;Prostatic Neoplasms - pathology;RECEPTORS;Receptors, Aryl Hydrocarbon - physiology;secretion;Signal Transduction - physiology;TRANSCRIPTION FACTORS;vascular endothelial growth factor A;Vascular Endothelial Growth Factor A - antagonists & inhibitors;Vascular Endothelial Growth Factor A - biosynthesis;Vascular Endothelial Growth Factor A - genetics;VEGF
日期:	2013-08-02
上傳時間:	2026-04-23 11:11:45 (UTC+8)
出版者:	Academic Press Inc.;United States: Elsevier Inc
摘要:	摘要： •LPA-induced VEGF-A expression was regulated by HIF-1α and ARNT.•PI3K mediated LPA-induced VEGF-A expression.•AHR signaling inhibited LPA-induced VEGF-A expression in PC-3 cells. Lysophosphatidic acid (LPA) is a lipid growth factor with multiple biological functions and has been shown to stimulate cancer cell secretion of vascular endothelial growth factor-A (VEGF-A) and trigger angiogenesis. Hypoxia-inducible factor-1 (HIF-1), a heterodimer consisting of HIF-1α and HIF-1β (also known as aromatic hydrocarbon receptor nuclear translocator (ARNT)) subunits, is an important regulator of angiogenesis in prostate cancer (PC) through the enhancement of VEGF-A expression. In this study, we first confirmed the ability of LPA to induce VEGF-A expression in PC-3 cells and then validated that LPA-induced VEGF-A expression was regulated by HIF-1α and ARNT through phosphatidylinositol 3-kinase activation. Aromatic hydrocarbon receptor (AHR), a receptor for dioxin-like compounds, functions as a transcription factor through dimerization with ARNT and was found to inhibit prostate carcinogenesis and vanadate-induced VEGF-A production. Since ARNT is a common dimerization partner of AHR and HIF-1α, we hypothesized that AHR might suppress LPA-induced VEGF-A expression in PC-3 cells by competing with HIF-1α for ARNT. Here we demonstrated that overexpression and ligand activation of AHR inhibited HIF-1-mediated VEGF-A induction by LPA treatment of PC-3 cells. In conclusion, our results suggested that AHR activation may inhibit LPA-induced VEGF-A expression in PC-3 cells by attenuating HIF-1α signaling, and subsequently, suppressing angiogenesis and metastasis of PC. These results suggested that AHR presents a potential therapeutic target for the prevention of PC metastasis. 其他題名： Biochem Biophys Res Commun 出版者： United States: Elsevier Inc 出版日期： 2013-08-02 出處： Biochemical and Biophysical Research Communications, 2013-08, Vol.437 (3), p.440-445 版權： 2013 The Authors 版權： Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved. 識別號： ISSN: 0006-291X 識別號： ISSN: 1090-2104 識別號： EISSN: 1090-2104 識別號： DOI: 10.1016/j.bbrc.2013.06.098 識別號： PMID: 23831623
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