Abstract
AhR is an environmental response gene that mediates cellular responses to a variety of xenobiotic compounds that frequently function as AhR ligands. Many AhR ligands are classified as carcinogens or pro-carcinogens. Thus, AhR itself acts as a major mediator of the carcinogenic effect of many xenobiotics in vivo. In this concise review, mechanisms by which AhR trans-activates downstream target gene expression, modulates immune responses, and mediates malignant transformation and tumor development are discussed. Moreover, activation of AhR by post-translational modifications and crosstalk with other transcription factors or signaling pathways are also summarized.
Keywords: Aryl hydrocarbon receptor, xenobiotics, carcinogenesis, transcription factor, post-translation modification, review.
Graphical Abstract
[1]
Poland A, Glover E. Genetic expression of aryl-hydrocarbon hydroxylase by 2,3,7,8-tetrachlorodibenzo-para-dioxin - evidence for a receptor mutation in genetically non-responsive mice. Mol Pharmacol 1975; 11(4): 389-98.
[2]
Poland A, Glover E. 2,3,7,8-tetrachlorodibenzo-p-dioxin- segregation of toxicity with the ah locus. Mol Pharmacol 1980; 17(1): 86-94.
[3]
Carlstedtduke JMB, Harnemo UB, Högberg B, Gustafsson JA. Interaction of the hepatic receptor protein for 2,3,7,8-tetrachlorodibenzo-para-dioxin with DNA. Biochim Biophys Acta 1981; 672(2): 131-41.
[4]
Greenlee WF, Poland A. Nuclear uptake of 2,3,7,8-tetrachlorodibenzo-para-dioxin in c57bl-6j and dba-2j mice - role of the hepatic cytosol receptor protein. J Biol Chem 1979; 254(19): 9814-21.
[5]
Gudas JM, Karenlampi SO, Hankinson O. Intracellular location of the ah receptor. J Cell Physiol 1986; 128(3): 441-8.
[6]
Hoffman EC, Reyes H, Chu FF, et al. Cloning of a factor required for activity of the ah (dioxin) receptor. Science 1991; 252(5008): 954-8.
[7]
Burbach KM, Poland A, Bradfield CA. Cloning of the ah-receptor cdna reveals a distinctive ligand-activated Transcription Factor. Proc Natl Acad Sci USA 1992; 89(17): 8185-9.
[8]
Ema M, Sogawa K, Watanabe N, et al. Cdna cloning and structure of mouse putative ah receptor. Biochem Biophys Res Commun 1992; 184(1): 246-53.
[9]
Hahn ME. Aryl hydrocarbon receptors: diversity and evolution. Chem Biol Interact 2002; 141(1-2): 131-60.
[10]
Wernet MF, Mazzoni EO, Çelik A, et al. Stochastic spineless expression creates the retinal mosaic for colour vision. Nature 2006; 440(7081): 174-80.
[11]
Duncan DM, Burgess EA, Duncan I. Control of distal antennal identity and tarsal development in Drosophila by spineless-aristapedia, a homolog of the mammalian dioxin receptor. Genes Dev 1998; 12(9): 1290-303.
[12]
Sutter TR, Greenlee WF. Classification of members of the ah gene battery. Chemosphere 1992; 25(1-2): 223-6.
[13]
Veldhoen M, Hirota K, Christensen J, O’Garra A, Stockinger B. Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells. J Exp Med 2009; 206(1): 43-9.
[14]
Robles R, Morita Y, Mann KK, et al. The aryl hydrocarbon receptor, a basic helix-loop-helix transcription factor of the PAS gene family, is required for normal ovarian germ cell dynamics in the mouse. Endocrinology 2000; 141(1): 450-3.
[15]
Lahvis GP, Pyzalski RW, Glover E, et al. The aryl hydrocarbon receptor is required for developmental closure of the ductus venosus in the neonatal mouse. Mol Pharmacol 2005; 67(3): 714-20.
[16]
Funatake CJ, Marshall NB, Steppan LB, Mourich DV, Kerkvliet NI. Cutting edge: Activation of the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin generates a population of CD4(+)CD25(+) cells with characteristics of regulatory T cells. J Immunol 2005; 175(7): 4184-8.
[17]
Swanson HI, Bradfield CA. The Ah-Receptor - Genetics, Structure and Function. Pharmacogenetics 1993; 3(5): 213-0.
[18]
Hubbard TD, Murray IA, Bisson WH, et al. Divergent ah receptor ligand selectivity during hominin evolution. Mol Biol Evol 2016; 33(10): 2648-58.
[19]
Walker NJ, Crockett PW, Nyska A, et al. Dose-additive carcinogenicity of a defined mixture of “dioxin-like compounds”. Environ Health Perspect 2005; 113(1): 43-8.
[20]
Loyola-Sepulveda R, Salamanca MO, Gutiérrez-Baeza F, et al. Contributions of dioxins and furans to the urban sediment signature: The role of atmospheric particles. Sci Total Environ 2018; 615: 751-60.
[21]
Vanmiller JP, Lalich JJ, Allen JR. Increased incidence of neoplasms in rats exposed to low-levels of 2,3,7,8-tetrachlorodibenzo-para-dioxin. Chemosphere 1977; 6(10): 625-32.
[22]
Kociba RJ, Keyes DG, Beyer JE, et al. Results of a 2-year chronic toxicity and oncogenicity study of 2,3,7,8-tetrachlorodibenzo-para-dioxin in rats. Toxicol Appl Pharmacol 1978; 46(2): 279-303.
[23]
Huff JE, Salmon AG, Hooper NK, Zeise L. Long-Term carcinogenesis studies on 2,3,7,8-tetrachlorodibenzo-para-dioxin and hexachlorodibenzo-para-dioxins. Cell Biol Toxicol 1991; 7(1): 67-94.
[24]
Reggiani G. Acute human exposure to tcdd in seveso, Italy. J Toxicol Environ Health 1980; 6(1): 27-43.
[25]
Bertazzi PA, Zocchetti C, Guercilena S, et al. Dioxin exposure and cancer risk: A 15-year mortality study after the “Seveso accident”. Epidemiol 1997; 8(6): 646-52.
[27]
Rahman MM, Shon Z-H, Ma C-J, et al. Partitioning of dioxins (PCDDs/Fs) in ambient air at urban residential locations. Int J Environ Sci Technol 2014; 11(7): 1897-910.
[28]
Hebert CD, Harris MW, Elwell MR, Birnbaum LS. Relative toxicity and tumor-promoting ability of 2,3,7,8-tetrachlorodibenzo-para-dioxin (tcdd), 2,3,4,7,8-pentachlorodibenzofuran (pcdf), and 1,2,3,4,7,8-hexachlorodibenzofuran (hcdf) in hairless mice. Toxicol Appl Pharmacol 1990; 102(2): 362-77.
[29]
Van den Berg M, Birnbaum LS, Denison M, et al. The 2005 world health organization reevaluation of human and mammalian toxic equivalency factors for dioxins and dioxin-like compounds. Toxicol Sci 2006; 93(2): 223-41.
[30]
Pesatori AC, Consonni D, Rubagotti M, Grillo P, Bertazzi PA. Cancer incidence in the population exposed to dioxin after the “Seveso accident”: twenty years of follow-up. Environ Health 2009; 15(8): 39.
[31]
FleschJanys D. Exposure to polychlorinated dioxins and furans (PCDD/F) and mortality in a cohort of workers from a herbicide-producing plant in Hamburg, Federal Republic of Germany - Reply. American J Epidemiol 1997; 146(4): 362-3.
[32]
Boers D, Portengen L, Bueno-de-Mesquita HB, Heederik D, Vermeulen R. Cause-specific mortality of Dutch chlorophenoxy herbicide manufacturing workers. Occupational Environ Med 2010; 67(1): 24-31.
[33]
Zhang YX, Tao S. Global atmospheric emission inventory of polycyclic aromatic hydrocarbons (PAHs) for 2004. Atmospheric Environ 2009; 43(4): 812-9.
[34]
Evangelou A, Karkabounas S, Kalpouzos G. Comparison of the therapeutic effects of two vanadium complexes administered at low doses on benzo[a]pyrene-induced malignant tumors in rats. Cancer Lett 1997; 119(2): 221-5.
[35]
Ashurst SW, Cohen GM, Nesnow S, DiGiovanni J, Slaga TJ. Formation of benzo(a)pyrene dna adducts and their relationship to tumor initiation in mouse epidermis. Cancer Res 1983; 43(3): 1024-9.
[36]
Guerreiro CBB, Horálek J, de Leeuw F, Couvidat F. Benzo(a)pyrene in Europe: Ambient air concentrations, population exposure and health effects. Environ Pollut 2016; 214: 657-67.
[37]
Verma N, Pink M, Rettenmeier AW, Schmitz-Spanke S. Review on proteomic analyses of benzo[a]pyrene toxicity. Proteomics 2012; 12(11): 1731-55.
[38]
Mumford JL, Li X, Hu F, Lu XB, Chuang JC. Human exposure and dosimetry of polycyclic aromatic hydrocarbons in urine from Xuan Wei, China with high lung cancer mortality associated with exposure to unvented coal smoke. Carcinogenesis 1995; 16(12): 3031-6.
[39]
Armstrong B, Hutchinson E, Unwin J, Fletcher T. Lung cancer risk after exposure to polycyclic aromatic hydrocarbons: A review and meta-analysis. Environ Health Perspect 2004; 112(9): 970-8.
[40]
Kim KH, Jahan SA, Kabir E, Brown RJ. A review of airborne polycyclic aromatic hydrocarbons (PAHs) and their human health effects. Environ Int 2013; 60: 71-80.
[41]
Tholander J, Bergman J. Synthesis of 6-formylindolo[3,2-b]carbazole, an extremely potent ligand for the aryl hydrogen (Ah) receptor. Tetrahedron Lett 1998; 39(12): 1619-22.
[42]
Oberg M, Bergander L, Håkansson H, Rannug U, Rannug A. Identification of the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole, in cell culture medium, as a factor that controls the background aryl hydrocarbon receptor activity. Toxicol Sci 2005; 85(2): 935-43.
[43]
Jeong KT, Hwang SJ, Oh GS, Park JH. FICZ, a Tryptophan photoproduct, suppresses pulmonary eosinophilia and Th2-type cytokine production in a mouse model of ovalbumin-induced allergic asthma. Int Immunopharmacol 2012; 13(4): 377-85.
[44]
Dantzer R, O’Connor JC, Lawson MA, Kelley KW. Inflammation-associated depression: From serotonin to kynurenine. Psychoneuroendocrinol 2011; 36(3): 426-36.
[45]
Mandi Y, Vecsei L. The kynurenine system and immunoregulation. J Neural Transm 2012; 119(2): 197-209.
[46]
DiNatale BC, Murray IA, Schroeder JC, et al. Kynurenic acid is a potent endogenous aryl hydrocarbon receptor ligand that synergistically induces interleukin-6 in the presence of inflammatory signaling. Toxicol Sci 2010; 115(1): 89-97.
[47]
Opitz CA, Litzenburger UM, Sahm F, et al. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature 2011; 478(7368): 197-203.
[48]
Pilotte L, Larrieu P, Stroobant V, et al. Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase. Proc Natl Acad Sci USA 2012; 109(7): 2497-502.
[49]
Zuo H, Ueland PM, Ulvik A, et al. Plasma biomarkers of inflammation, the kynurenine pathway, and risks of all-cause, cancer, and cardiovascular disease mortality. Am J Epidemiol 2016; 183(4): 249-58.
[50]
Suzuki Y, Suda T, Furuhashi K, et al. Increased serum kynurenine/tryptophan ratio correlates with disease progression in lung cancer. Lung Cancer 2010; 67(3): 361-5.
[51]
Nguyen LP, Bradfield CA. The search for endogenous activators of the aryl hydrocarbon receptor. Chem Res Toxicol 2008; 21(1): 102-16.
[52]
Bergander L, Wincent E, Rannug A, et al. Metabolic fate of the Ah receptor ligand 6-formylindolo[3,2-b]carbazole. Chem Biolog Interact 2004; 149(2-3): 151-64.
[53]
Kawajiri K, Kobayashi Y, Ohtake F, et al. Aryl hydrocarbon receptor suppresses intestinal carcinogenesis in Apc > Min/+ mice with natural ligands. Proc Natl Acad Sci USA 2009; 106(32): 13481-6.
[54]
Revel A, Raanani H, Younglai E, et al. Resveratrol, a natural aryl hydrocarbon receptor antagonist, protects lung from DNA damage and apoptosis caused by benzo[a]pyrene. J Appl Toxicol 2003; 23(4): 255-61.
[55]
Casper RF, Quesne M, Rogers IM, et al. Resveratrol has antagonist activity on the aryl hydrocarbon receptor: Implications for prevention of dioxin toxicity. Mol Pharmacol 1999; 56(4): 784-90.
[56]
Murray IA, Patterson AD, Perdew GH. Aryl hydrocarbon receptor ligands in cancer: friend and foe. Nature Rev Cancer 2014; 14(12): 801-14.
[57]
Nebert DW, Dalton TP. The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis. Nat Rev Cancer 2006; 6(12): 947-60.
[58]
Nebert DW, Dalton TP, Okey AB, Gonzalez FJ. Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer. J Biol Chem 2004; 279(23): 23847-50.
[59]
Joseph P, Jaiswal AK. Nad(p)h-quinone oxidoreductase(1) (dt diaphorase) specifically prevents the formation of benzo[a]pyrene quinone-dna adducts generated by cytochrome p4501a1 and p450 reductase. Proc Natl Acad Sci USA 1994; 91(18): 8413-7.
[60]
Gelboin HV. Benzo[a]pyrene metabolism, activation, and carcinogenesis - role and regulation of mixed-function oxidases and related enzymes. Physiol Rev 1980; 60(4): 1107-66.
[61]
de Waard PWJ, de Kok TM, Maas LM, et al. Influence of TCDD and natural Ah receptor agonists on benzo[a]pyrene-DNA adduct formation in the Caco-2 human colon cell line. Mutagenesis 2008; 23(1): 67-73.
[62]
Troxel CM, Buhler DR, Hendricks JD, Bailey GS, et al. CYP1A induction by beta-naphthoflavone, Aroclor 1254, and 2,3,7,8-tetrachlorodibenzo-p-dioxin and its influence on aflatoxin B-1 metabolism and DNA adduction in zebrafish (Danio rerio). Toxicol Appl Pharmacol 1997; 146(1): 69-78.
[63]
Lin PH, Lin CH, Huang CC, Fang JP, Chuang MC, et al. 2,3,7,8-tetrachlorodibenzo-p-dioxin modulates the induction of DNA strand breaks and poly(ADP-ribose) polymerase-1 activation by 17 beta-estradiol in human breast carcinoma cells through alteration of CYP1A1 and CYP1B1 expression. Chem Res Toxicol 2008; 21(7): 1337-47.
[64]
Hakk H, Larsen G, Feil V. Tissue distribution, excretion, and metabolism of 1,2,7,8-tetrachlorodibenzo-p-dioxin in the rat. Chemosphere 2001; 42(8): 975-83.
[65]
Sorg O, Zennegg M, Schmid P, et al. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) poisoning in Victor Yushchenko: identification and measurement of TCDD metabolites. Lancet 2009; 374(9696): 1179-85.
[66]
Uno S, Dalton TP, Derkenne S, et al. Oral exposure to benzo[a] pyrene in the mouse: Detoxication by inducible cytochrome P450 is more important than metabolic activation. Mol Pharmacol 2004; 65(5): 1225-37.
[67]
Harrigan JA, McGarrigle BP, Sutter TR, Olson JR. Tissue specific induction of cytochrome P450 (CYP) 1A1 and 1B1 in rat liver and lung following in vitro (tissue slice) and in vivo exposure to benzo(a)pyrene. Toxicol In Vitro 2006; 20(4): 426-38.
[68]
Dragin N, Shi Z, Madan R, et al. Phenotype of the Cyp1a1/1a2/1b1(-/-) triple-knockout mouse. Mol Pharmacol 2008; 73(6): 1844-56.
[69]
Wyde ME, Wong VA. Induction of hepatic 8-oxo-deoxyguanosine adducts by 2,3,7,8-tetrachlorodibenzo-p-dioxin in Sprague-Dawley rats is female-specific and estrogen-dependent. Chem Res Toxicol 2001; 14(7): 849-55.
[70]
Park JYK, Shigenaga MK, Ames BN. Induction of cytochrome P4501A1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin or indolo(3,2-b)carbazole is associated with oxidative DNA damage. Proc Natl Acad Sci USA 1996; 93(6): 2322-7.
[71]
Knerr S, Schaefer J, Both S, Mally A, Dekant W, Schrenk D, et al. 2,3,7,8-Tetrachlorodibenzo-p-dioxin induced cytochrome P450s alter the formation of reactive oxygen species in liver cells. Mol Nutr Food Res 2006; 50(4-5): 378-84.
[72]
Nguyen NT, Hanieh H, Nakahama T, Kishimoto T. The roles of aryl hydrocarbon receptor in immune responses. Int Immunol 2013; 25(6): 335-43.
[73]
Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010; 140(6): 883-99.
[74]
Kennedy GD, Nukaya M, Moran SM, et al. Liver tumor promotion by 2,3,7,8-tetrachlorodibenzo-p-dioxin is dependent on the aryl hydrocarbon receptor and tnf/il-1 receptors. Toxicol Sci 2014; 140(1): 135-43.
[75]
Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 2011; 1813(5): 878-88.
[76]
DiNatale BC, Schroeder JC, Francey LJ, Kusnadi A, Perdew GH. Mechanistic insights into the events that lead to synergistic induction of interleukin 6 transcription upon activation of the aryl hydrocarbon receptor and inflammatory signaling. J Biol Chem 2010; 285(32): 24388-97.
[77]
DiNatale BC, Schroeder JC, Perdew GH. Ah receptor antagonism inhibits constitutive and cytokine inducible il6 production in head and neck tumor cell lines. Mol Carcinogenesis 2011; 50(3): 173-83.
[78]
Chen PH, Chang H, Chang JT, Lin P. Aryl hydrocarbon receptor in association with RelA modulates IL-6 expression in non-smoking lung cancer. Oncogene 2012; 31(20): 2555-65.
[79]
Cedeno-Laurent F, Opperman M, Barthel SR, Kuchroo VK, Dimitroff CJ. Galectin-1 triggers an immunoregulatory signature in th cells functionally defined by il-10 expression. J Immunol 2012; 188(7): 3127-37.
[80]
Luo YH, Kuo YC, Tsai MH, et al. Interleukin-24 as a target cytokine of environmental aryl hydrocarbon receptor agonist exposure in the lung. Toxicol Appl Pharmacol 2017; 324: 1-11.
[81]
Martey CA, Baglole CJ, Gasiewicz TA, Sime PJ, Phipps RP. The aryl hydrocarbon receptor is a regulator of cigarette smoke induction of the cyclooxygenase and prostaglandin pathways in human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol 2005; 289(3): L391-9.
[82]
Degner SC, Papoutsis AJ, Selmin O, Romagnolo DF. Targeting of aryl hydrocarbon receptor-mediated activation of cyclooxygenase-2 expression by the indole-3-carbinol metabolite 3,3 '-diindolylmethane in breast cancer cells. J Nutr 2009; 139(1): 26-32.
[83]
Huang YH, Cao Y-F, Jiang Z-Y, Zhang S, Gao F, et al. Th22 cell accumulation is associated with colorectal cancer development. World J Gastroenterol 2015; 21(14): 4216-24.
[84]
Shin JH, Zhang L, Murillo-Sauca O, et al. Modulation of natural killer cell antitumor activity by the aryl hydrocarbon receptor. Proc Natl Acad Sci USA 2013; 110(30): 12391-6.
[85]
Ronnekleiv-Kelly SM, Nukaya M, Díaz-Díaz CJ, et al. Aryl hydrocarbon receptor-dependent apoptotic cell death induced by the flavonoid chrysin in human colorectal cancer cells. Cancer Lett 2016; 370(1): 91-9.
[86]
Salisbury TB, Tomblin JK, Primerano DA, et al. Endogenous aryl hydrocarbon receptor promotes basal and inducible expression of tumor necrosis factor target genes in MCF-7 cancer cells. Biochem Pharmacol 2014; 91(3): 390-9.
[87]
Narayanan GA, Murray IA, Krishnegowda G, Amin S, Perdew GH. Selective aryl hydrocarbon receptor modulator-mediated repression of cd55 expression induced by cytokine exposure. J Pharmacol Exp Ther 2012; 342(2): 345-55.
[88]
Kharat I, Saatcioglu F. Antiestrogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin are mediated by direct transcriptional interference with the liganded estrogen receptor - Cross-talk between aryl hydrocarbon- and estrogen-mediated signaling. J Biol Chem 1996; 271(18): 10533-7.
[89]
Vessey M, Baron J, Doll R, McPherson K, Yeates D. Oral-contraceptives and breast-cancer-final report of an epidemiological-study. Br J Cancer 1983; 47(4): 455-62.
[90]
Wormke M, Stoner M, Saville B, Safe S. Crosstalk between estrogen receptor alpha and the aryl hydrocarbon receptor in breast cancer cells involves unidirectional activation of proteasomes. Febs Lett 2000; 478(1-2): 109-12.
[91]
Ahmed S, Valen E, Sandelin A, Matthews J. Dioxin increases the interaction between aryl hydrocarbon receptor and estrogen receptor alpha at human promoters. Toxicol Sci 2009; 111(2): 254-66.
[92]
Lo R. Matthews j. The aryl hydrocarbon receptor and estrogen receptor alpha differentially modulate nuclear factor erythroid-2-related factor 2 transactivation in MCF-7 breast cancer cells. Toxicol Appl Pharmacol 2013; 270(2): 139-48.
[93]
Hsu EL, Yoon D, Choi HH, et al. A proposed mechanism for the protective effect of dioxin against breast cancer. Toxicol Sci 2007; 98(2): 436-44.
[94]
Ohtake F, Baba A, Takada I, et al. Dioxin receptor is a ligand-dependent E3 ubiquitin ligase. Nature 2007; 446(7135): 562-6.
[95]
Ide H, Lu J, Yu J, et al. Aryl hydrocarbon receptor signaling involved in the invasiveness of LNCaP cells. Human Cell 2017; 30(2): 133-9.
[96]
Morrow D, Qin C, Smith R 3rd, Safe S, et al. Aryl hydrocarbon receptor-mediated inhibition of LNCaP prostate cancer cell growth and hormone-induced transactivation. J Steroid Biochem Mol Biol 2004; 88(1): 27-36.
[97]
Richmond O, Ghotbaddini M, Allen C, et al. The aryl hydrocarbon receptor is constitutively active in advanced prostate cancer cells. Plos One 2014; 9(4): e95058.
[98]
Kim DW, Gazourian L, Quadri SA, et al. The RelA NF-kappa B subunit and the aryl hydrocarbon receptor (AhR) cooperate to transactivate the c-myc promoter in mammary cells. Oncogene 2000; 19(48): 5498-506.
[99]
Vogel CFA, Sciullo E, Li W, et al. ReIB, a new partner of aryl hydrocarbon receptor-mediated transcription. Mol Endocrinol 2007; 21(12): 2941-55.
[100]
Silginer M, Burghardt I, Gramatzki D, et al. The aryl hydrocarbon receptor links integrin signaling to the TGF-beta pathway. Oncogene 2016; 35(25): 3260-71.
[101]
Koch DC, Jang HS, O’Donnell EF, et al. Anti-androgen flutamide suppresses hepatocellular carcinoma cell proliferation via the aryl hydrocarbon receptor mediated induction of transforming growth factor-beta 1. Oncogene 2015; 34(50): 6092-04.
[102]
Chang XQ, Fan Y, Karyala S, et al. Ligand-independent regulation of transforming growth factor beta 1 expression and cell cycle progression by the aryl hydrocarbon receptor. Mol Cellular Biol 2007; 27(17): 6127-39.
[103]
Xu DZ, Yao Y, Lu L, Costa M, Dai W. Plk3 functions as an essential component of the hypoxia regulatory pathway by direct phosphorylation of hif-1 alpha. J Biol Chem 2010; 285(50): 38944-50.
[104]
Belozerov VE, Van Meir EG. Hypoxia inducible factor-1: a novel target for cancer therapy. Anticancer Drugs 2005; 16(9): 901-9.
[105]
Yang YL, Bai J, Shen R, et al. Polo-like kinase 3 functions as a tumor suppressor and is a negative regulator of hypoxia-inducible factor-1 alpha under hypoxic conditions. Cancer Res 2008; 68(11): 4077-85.
[106]
Pan JJ, Chang QS, Wang X, et al. Activation of Akt/GSK3 beta and Akt/Bcl-2 signaling pathways in nickel-transformed BEAS-2B cells. Int J Oncol 2011; 39(5): 1285-94.
[107]
Gassmann M, Kvietikova I, Rolfs A, Wenger RH, et al. Oxygen- and dioxin-regulated gene expression in mouse hepatoma cells. Kidney Int 1997; 51(2): 567-74.
[108]
Gradin K, McGuire J, Wenger RH, et al. Functional interference between hypoxia and dioxin signal transduction pathways: Competition for recruitment of the Arnt transcription factor. Mol Cell Biol 1996; 16(10): 5221-31.
[109]
Chan WK, Yao G, Gu YZ, Bradfield CA. Cross-talk between the aryl hydrocarbon receptor and hypoxia inducible factor signaling pathways-Demonstration of competition and compensation. J Biol Chem 1999; 274(17): 12115-23.
[110]
Nie MH, Blankenship AL, Giesy JP. Interactions between aryl hydrocarbon receptor (AhR) and hypoxia signaling pathways. Environ Toxicol Pharmacol 2001; 10(1-2): 17-27.
[111]
Ichihara S, Yamada Y, Ichihara G, et al. A role for the aryl hydrocarbon receptor in regulation of ischemia-induced angiogenesis. Arterioscler Thromb Vasc Biol 2007; 27(6): 1297-304.
[112]
Weiss C, Faust D, Schreck I, et al. TCDD deregulates contact inhibition in rat liver oval cells via Ah receptor, JunD and cyclin A. Oncogene 2008; 27(15): 2198-207.
[113]
Li CH, Liu CW, Tsai CH, et al. Cytoplasmic aryl hydrocarbon receptor regulates glycogen synthase kinase 3 beta, accelerates vimentin degradation, and suppresses epithelial-mesenchymal transition in non-small cell lung cancer cells. Arch Toxicol 2017; 91(5): 2165-78.
[114]
Bessede A, Gargaro M, Pallotta MT, et al. Aryl hydrocarbon receptor control of a disease tolerance defence pathway. Nature 2014; 511(7508): 184-90.
[115]
Ikuta T, Kobayashi Y, Kawajiri K. Phosphorylation of nuclear localization signal inhibits the ligand-dependent nuclear import of aryl hydrocarbon receptor. Biochem Biophys Res Commun 2004; 317(2): 545-50.
[116]
Kido S, Fujihara M, Nomura K, et al. Molecular mechanisms of cadmium-induced fibroblast growth factor 23 upregulation in osteoblast-like cells. Toxicol Sci 2014; 139(2): 301-16.
[117]
Minsavage GD, Park SK, Gasiewicz TA. The aryl hydrocarbon receptor (AhR) tyrosine 9, a residue that is essential for AhR DNA binding activity, is not a phosphoresidue but augments AhR phosphorylation. J Biol Chem 2004; 279(20): 20582-93.
[119]
Ma Q, Baldwin KT. 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced degradation of aryl hydrocarbon receptor (AhR) by the ubiquitin-proteasome pathway-Role of the transcription activaton and DNA binding of AhR. J Biol Chem 2000; 275(12): 8432-8.
[120]
Xing XR, Bi H, Chang AK, et al. SUMOylation of AhR modulates its activity and stability through inhibiting its ubiquitination. J Cell Physiol 2012; 227(12): 3812-9.
[121]
Liebelt F, Vertegaal AC. Ubiquitin-dependent and independent roles of SUMO in proteostasis. Am J Physiol Cell Physiol 2016; 311(2): C284-96.
[122]
Antenos M, Casper RF, Brown TJ. Interaction with Nedd8, a ubiquitin-like protein, enhances the transcriptional activity of the aryl hydrocarbon receptor. J Biol Chem 2002; 277(46): 44028-34.
[123]
Jin UH, Lee SO, Pfent C, Safe S, et al. The aryl hydrocarbon receptor ligand omeprazole inhibits breast cancer cell invasion and metastasis. BMC Cancer 2014; 9(14): 498.
[124]
Brinkman AM, Wu J, Ersland K, Xu W. Estrogen receptor alpha and aryl hydrocarbon receptor independent growth inhibitory effects of aminoflavone in breast cancer cells. BMC Cancer 2014; 20(14): 344.
Article Metrics
68
8
2
1