https://scholars.lib.ntu.edu.tw/handle/123456789/377984
Title: | Aromatic hydrocarbon receptor inhibits lysophosphatidic acid-induced vascular endothelial growth factor-A expression in PC-3 prostate cancer cells | Authors: | Wu, P.-Y. Lin, Y.-C. Lan, S.-Y. Huang, Y.-L. Lee, H. HSIN-YU LEE |
Keywords: | AHR; HIF-1; LPA; VEGF | Issue Date: | 2013 | Journal Volume: | 437 | Journal Issue: | 3 | Start page/Pages: | 440-445 | Source: | Biochemical and Biophysical Research Communications | Abstract: | 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. ? 2013 The Authors. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-84880965149&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/377984 |
DOI: | 10.1016/j.bbrc.2013.06.098 | SDG/Keyword: | aromatic hydrocarbon receptor; lysophosphatidic acid; phosphatidylinositol 3 kinase; vanadic acid; vasculotropin A; article; cancer cell; carcinogenesis; controlled study; dimerization; enzyme activation; human; human cell; male; priority journal; prostate cancer; protein expression; AHR; HIF-1; LPA; VEGF; Angiogenesis Inducing Agents; Aryl Hydrocarbon Receptor Nuclear Translocator; Cell Line, Tumor; HEK293 Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lysophospholipids; Male; Neoplasm Metastasis; Neovascularization, Pathologic; Prostatic Neoplasms; Receptors, Aryl Hydrocarbon; Signal Transduction; Vascular Endothelial Growth Factor A |
Appears in Collections: | 生命科學系 |
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