Abstract
There is now mounting evidence that the aryl hydrocarbon receptor (AhR) plays an important role in physiologic responses such as development, cell cycle regulation, immune function and also malignant transformation in various tissues. The strong nuclear AhR expression is observed in the invasive phenotype, and an elevated nuclear AhR expression is associated with a poor prognosis of human prostate cancer. On the other hand, there are conflicting results that the AhR deficiency results in increased susceptibility to prostate tumors in mouse model. In the present study, we investigated AhR expression and its role in the growth and invasiveness of human prostate cancer cells. The AhR protein expression was detected in prostate cancer cell lines and human prostate cancer tissues. A small interfering RNA targeting AhR, constitutive active AhR expression vector, and AhR agonist and antagonist were used to moderate its expression and signaling. The induction of AhR signaling attenuated invasiveness of prostate cancer cells without affecting the cellular growth rate. These results suggest that AhR signaling in prostate cancer cells facilitates invasion of these cells, and modulation with this signaling can be a potential therapeutic target of invasive tumors.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- RT-PCR:
-
Reverse transcriptase-polymerase chain reaction
References
Beischlag TV, Luis Morales J, Hollingshead BD, Perdew GH. The aryl hydrocarbon receptor complex and the control of gene expression. Crit Rev Eukaryot Gene Expr. 2008;18:207–50.
Esser C. Biology and function of the aryl hydrocarbon receptor: report of an international and interdisciplinary conference. Arch Toxicol. 2012;86:1323–9.
Murray IA, Patterson AD, Perdew GH. Aryl hydrocarbon receptor ligands in cancer: friend and foe. Nat Rev Cancer. 2014;14:801–14.
Abdelrahim M, Smith R 3rd, Safe S. Aryl hydrocarbon receptor gene silencing with small inhibitory RNA differentially modulates Ah-responsiveness in MCF-7 and HepG2 cancer cells. Mol Pharmacol. 2003;63:1373–81.
Marlowe JL, Puga A. Aryl hydrocarbon receptor, cell cycle regulation, toxicity, and tumorigenesis. J Cell Biochem. 2005;96:1174–84.
Richmond O, Ghotbaddini M, Allen C, Walker A, Zahir S, Powell JB. The aryl hydrocarbon receptor is constitutively active in advanced prostate cancer cells. PLoS ONE. 2014;9:e95058.
Fritz WA, Lin TM, Cardiff RD, Peterson RE. The aryl hydrocarbon receptor inhibits prostate carcinogenesis in TRAMP mice. Carcinogenesis. 2007;28:497–505.
Benson JM, Shepherd DM. Dietary ligands of the aryl hydrocarbon receptor induce anti-inflammatory and immunoregulatory effects on murine dendritic cells. Toxicol Sci. 2011;124:327–38.
Bisson WH, Koch DC, O’Donnell EF, et al. Modeling of the aryl hydrocarbon receptor (AhR) ligand binding domain and its utility in virtual ligand screening to predict new AhR ligands. J Med Chem. 2009;52:5635–41.
Lawrence BP, Denison MS, Novak H, et al. Activation of the aryl hydrocarbon receptor is essential for mediating the anti-inflammatory effects of a novel low-molecular-weight compound. Blood. 2008;112:1158–65.
Jin UH, Lee SO, Pfent C, Safe S. The aryl hydrocarbon receptor ligand omeprazole inhibits breast cancer cell invasion and metastasis. BMC Cancer. 2014;14:498.
Jin UH, Kim SB, Safe S. Omeprazole inhibits pancreatic cancer cell invasion through a nongenomic aryl hydrocarbon receptor pathway. Chem Res Toxicol. 2015;28:907–18.
Moore RW, Fritz WA, Schneider AJ, et al. 2,3,7,8-Tetrachlorodibenzo-p-dioxin has both pro-carcinogenic and anti-carcinogenic effects on neuroendocrine prostate carcinoma formation in TRAMP mice. Toxicol Appl Pharmacol. 2016.
Singh SS, Hord NG, Perdew GH. Characterization of the activated form of the aryl hydrocarbon receptor in the nucleus of HeLa cells in the absence of exogenous ligand. Arch Biochem Biophys. 1996;329:47–55.
Cho YC, Zheng W, Jefcoate CR. Disruption of cell-cell contact maximally but transiently activates AhR-mediated transcription in 10T1/2 fibroblasts. Toxicol Appl Pharmacol. 2004;199:220–38.
Ikuta T, Kobayashi Y, Kawajiri K. Cell density regulates intracellular localization of aryl hydrocarbon receptor. J Biol Chem. 2004;279:19209–16.
Diry M, Tomkiewicz C, Koehle C, et al. Activation of the dioxin/aryl hydrocarbon receptor (AhR) modulates cell plasticity through a JNK-dependent mechanism. Oncogene. 2006;25:5570–4.
Peng TL, Chen J, Mao W, Song X, Chen MH. Aryl hydrocarbon receptor pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of matrix metalloproteinase-9. BMC Cell Biol. 2009;10:27.
Rico-Leo EM, Alvarez-Barrientos A, Fernandez-Salguero PM. Dioxin receptor expression inhibits basal and transforming growth factor beta-induced epithelial-to-mesenchymal transition. J Biol Chem. 2013;288:7841–56.
Abdelrahim M, Ariazi E, Kim K, et al. 3-Methylcholanthrene and other aryl hydrocarbon receptor agonists directly activate estrogen receptor alpha. Cancer Res. 2006;66:2459–67.
Ohtake F, Takeyama K, Matsumoto T, et al. Modulation of oestrogen receptor signalling by association with the activated dioxin receptor. Nature. 2003;423:545–50.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
We do not have any conflict of interest to disclose in this study.
Rights and permissions
About this article
Cite this article
Ide, H., Lu, Y., Yu, J. et al. Aryl hydrocarbon receptor signaling involved in the invasiveness of LNCaP cells. Human Cell 30, 133–139 (2017). https://doi.org/10.1007/s13577-016-0158-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13577-016-0158-2