Entry Name Chemical carcinogenesis - receptor activation - Peromyscus leucopus (white-footed mouse)
Description Carcinogenesis is a multistage process that consists of initiation, promotion, and progression stages. Chemicals or environmental factors may act at any of these stages to induce and/or enhance the carcinogenic process. Based on their mode-of-action, carcinogens can be classified as genotoxic or non-genotoxic. Genotoxic agent begins their action at the deoxyribonucleic acid (DNA) level, causing DNA damage through several mechanisms. Non-genotoxic carcinogens are chemicals that cause the development of tumors through multiple non-genotoxic events and epigenetic alterations without direct interaction with DNA. One non-genotoxic mechanism involves receptor activation. Biological mechanisms involving receptor activation fall into two broad categories: (i) those that involve cell surface receptors and some intracellular receptors that activate signal transduction pathways, resulting in biological responses, including gene transcription, and (ii) those that involve intracellular receptors that translocate into the nucleus and act as transcription factors regulating gene expression. Both classes of receptors can be involved in mechanisms of carcinogenesis.
Class Human Diseases; Cancer: overviewBRITE hierarchy
Pathway map pleu05207 Chemical carcinogenesis - receptor activation
Organism Peromyscus leucopus (white-footed mouse) [GN:
pleu ]
Gene 114680676 Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158 ]
114682408 Arnt; aryl hydrocarbon receptor nuclear translocator isoform X1 [KO:K09097 ]
114682786 Stat3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
114682811 Stat5a; signal transducer and activator of transcription 5A [KO:K11223 ]
114683299 Cacna1s; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
114684032 Pik3cd; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
114684157 Cacna1a; voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344 ]
114685418 Nr1i3; nuclear receptor subfamily 1 group I member 3 isoform X1 [KO:K08541 ]
114686204 Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851 ]
114686260 Notch2; LOW QUALITY PROTEIN: neurogenic locus notch homolog protein 2 [KO:K20994 ]
114688126 Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
114688966 Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649 ]
114689726 Creb5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
114690302 Chrna3; neuronal acetylcholine receptor subunit alpha-3 isoform X1 [KO:K04805 ]
114690303 Chrnb4; neuronal acetylcholine receptor subunit beta-4 [KO:K04815 ]
114691010 Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
114692733 Cacna1b; voltage-dependent N-type calcium channel subunit alpha-1B [KO:K04849 ]
114693559 Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
114694285 Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
114695335 Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
114695505 Chrna7; neuronal acetylcholine receptor subunit alpha-7 [KO:K04809 ]
114699201 Ppara; peroxisome proliferator-activated receptor alpha [KO:K07294 ]
114699702 Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
114699851 Tnfsf11; tumor necrosis factor ligand superfamily member 11 [KO:K05473 ]
114699988 Gnai3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630 ]
114700762 Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C isoform X8 [KO:K04850 ]
114700827 Atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
114701281 Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853 ]
114702001 Chrna9; neuronal acetylcholine receptor subunit alpha-9 [KO:K04810 ]
114703207 Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
114703850 Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
114704184 Chrna4; LOW QUALITY PROTEIN: neuronal acetylcholine receptor subunit alpha-4 [KO:K04806 ]
114705057 Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
114705300 Vegfa; vascular endothelial growth factor A isoform X1 [KO:K05448 ]
114705847 Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
114706924 Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
114706956 Cdc6; cell division control protein 6 homolog isoform X1 [KO:K02213 ]
114707907 Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048 ]
114707959 Chrnb2; LOW QUALITY PROTEIN: neuronal acetylcholine receptor subunit beta-2 [KO:K04813 ]
114708228 Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
114708968 Birc5; baculoviral IAP repeat-containing protein 5 isoform X1 [KO:K08731 ]
114710969 Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
119089216 Eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
Compound C03690 Bis(2-ethylhexyl)phthalate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
C07557 2,3,7,8-Tetrachlorodibenzodioxin
C08150 Medroxyprogesterone acetate
C14240 Di(2-ethylhexyl) adipate
C14573 3,3',4,4',5-Pentachlorobiphenyl
C16453 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone
Reference Authors Luch A.
Title Nature and nurture - lessons from chemical carcinogenesis.
Journal Reference Authors Hernandez LG, van Steeg H, Luijten M, van Benthem J
Title Mechanisms of non-genotoxic carcinogens and importance of a weight of evidence approach.
Journal Reference Authors Wu CH, Lee CH, Ho YS
Title Nicotinic acetylcholine receptor-based blockade: applications of molecular targets for cancer therapy.
Journal Reference Authors Schuller HM
Title Is cancer triggered by altered signalling of nicotinic acetylcholine receptors?
Journal Reference Authors Singh S, Pillai S, Chellappan S
Title Nicotinic acetylcholine receptor signaling in tumor growth and metastasis.
Journal Reference Authors Cheng WL, Chen KY, Lee KY, Feng PH, Wu SM
Title Nicotinic-nAChR signaling mediates drug resistance in lung cancer.
Journal Reference Authors Grando SA
Title Connections of nicotine to cancer.
Journal Reference Authors Schaal C, Chellappan SP
Title Nicotine-mediated cell proliferation and tumor progression in smoking-related cancers.
Journal Reference Authors Improgo MR, Tapper AR, Gardner PD
Title Nicotinic acetylcholine receptor-mediated mechanisms in lung cancer.
Journal Reference Authors Egleton RD, Brown KC, Dasgupta P
Title Nicotinic acetylcholine receptors in cancer: multiple roles in proliferation and inhibition of apoptosis.
Journal Reference Authors Xue J, Yang S, Seng S
Title Mechanisms of Cancer Induction by Tobacco-Specific NNK and NNN.
Journal Reference Authors Wen J, Fu JH, Zhang W, Guo M
Title Lung carcinoma signaling pathways activated by smoking.
Journal Reference Authors Gankhuyag N, Lee KH, Cho JY
Title The Role of Nitrosamine (NNK) in Breast Cancer Carcinogenesis.
Journal Reference Authors Guo J, Kim D, Gao J, Kurtyka C, Chen H, Yu C, Wu D, Mittal A, Beg AA, Chellappan SP, Haura EB, Cheng JQ
Title IKBKE is induced by STAT3 and tobacco carcinogen and determines chemosensitivity in non-small cell lung cancer.
Journal Reference Authors Chen RJ, Ho YS, Guo HR, Wang YJ
Title Long-term nicotine exposure-induced chemoresistance is mediated by activation of Stat3 and downregulation of ERK1/2 via nAChR and beta-adrenoceptors in human bladder cancer cells.
Journal Reference Authors Lee CH, Chang YC, Chen CS, Tu SH, Wang YJ, Chen LC, Chang YJ, Wei PL, Chang HW, Chang CH, Huang CS, Wu CH, Ho YS
Title Crosstalk between nicotine and estrogen-induced estrogen receptor activation induces alpha9-nicotinic acetylcholine receptor expression in human breast cancer cells.
Journal Reference Authors Yager JD, Davidson NE
Title Estrogen carcinogenesis in breast cancer.
Journal Reference Authors Murata M, Kang JH
Title Bisphenol A (BPA) and cell signaling pathways.
Journal Reference Authors Wang Z, Liu H, Liu S
Title Low-Dose Bisphenol A Exposure: A Seemingly Instigating Carcinogenic Effect on Breast Cancer.
Journal Reference Authors Sauer SJ, Tarpley M, Shah I, Save AV, Lyerly HK, Patierno SR, Williams KP, Devi GR
Title Bisphenol A activates EGFR and ERK promoting proliferation, tumor spheroid formation and resistance to EGFR pathway inhibition in estrogen receptor-negative inflammatory breast cancer cells.
Journal Reference Authors Chen QY, Costa M
Title PI3K/Akt/mTOR Signaling Pathway and the Biphasic Effect of Arsenic in Carcinogenesis.
Journal Reference Authors Pedroza DA, Subramani R, Lakshmanaswamy R
Title Classical and Non-Classical Progesterone Signaling in Breast Cancers.
Journal Reference Authors Finlay-Schultz J, Sartorius CA
Title Steroid hormones, steroid receptors, and breast cancer stem cells.
Journal Reference Authors Valadez-Cosmes P, Vazquez-Martinez ER, Cerbon M, Camacho-Arroyo I
Title Membrane progesterone receptors in reproduction and cancer.
Journal Reference Authors Chen B, Ye P, Chen Y, Liu T, Cha JH, Yan X, Yang WH
Title Involvement of the Estrogen and Progesterone Axis in Cancer Stemness: Elucidating Molecular Mechanisms and Clinical Significance.
Journal Reference Authors Murray IA, Patterson AD, Perdew GH
Title Aryl hydrocarbon receptor ligands in cancer: friend and foe.
Journal Reference Authors Larigot L, Juricek L, Dairou J, Coumoul X
Title AhR signaling pathways and regulatory functions.
Journal Reference Authors Kawajiri K, Fujii-Kuriyama Y
Title The aryl hydrocarbon receptor: a multifunctional chemical sensor for host defense and homeostatic maintenance.
Journal Reference Authors Hidaka T, Fujimura T, Aiba S
Title Aryl Hydrocarbon Receptor Modulates Carcinogenesis and Maintenance of Skin Cancers.
Journal Reference Authors Mandal PK
Title Dioxin: a review of its environmental effects and its aryl hydrocarbon receptor biology.
Journal Reference Authors Miret NV, Pontillo CA, Zarate LV, Kleiman de Pisarev D, Cocca C, Randi AS
Title Impact of endocrine disruptor hexachlorobenzene on the mammary gland and breast cancer: The story thus far.
Journal Reference Authors Zarate LV, Pontillo CA, Espanol A, Miret NV, Chiappini F, Cocca C, Alvarez L, de Pisarev DK, Sales ME, Randi AS
Title Angiogenesis signaling in breast cancer models is induced by hexachlorobenzene and chlorpyrifos, pesticide ligands of the aryl hydrocarbon receptor.
Journal Reference Authors L'Heritier F, Marques M, Fauteux M, Gaudreau L
Title Defining molecular sensors to assess long-term effects of pesticides on carcinogenesis.
Journal Reference Authors Kitamura M, Kasai A
Title Cigarette smoke as a trigger for the dioxin receptor-mediated signaling pathway.
Journal Reference Authors Smith MT, Guyton KZ, Gibbons CF, Fritz JM, Portier CJ, Rusyn I, DeMarini DM, Caldwell JC, Kavlock RJ, Lambert PF, Hecht SS, Bucher JR, Stewart BW, Baan RA, Cogliano VJ, Straif K
Title Key Characteristics of Carcinogens as a Basis for Organizing Data on Mechanisms of Carcinogenesis.
Journal Reference Authors Yoshinari K
Title Role of Nuclear Receptors PXR and CAR in Xenobiotic-Induced Hepatocyte Proliferation and Chemical Carcinogenesis.
Journal Reference Authors Yoo HS, Cichocki JA, Kim S, Venkatratnam A, Iwata Y, Kosyk O, Bodnar W, Sweet S, Knap A, Wade T, Campbell J, Clewell HJ, Melnyk SB, Chiu WA, Rusyn I
Title The Contribution of Peroxisome Proliferator-Activated Receptor Alpha to the Relationship Between Toxicokinetics and Toxicodynamics of Trichloroethylene.
Journal Reference Authors Pyper SR, Viswakarma N, Yu S, Reddy JK
Title PPARalpha: energy combustion, hypolipidemia, inflammation and cancer.
Journal Reference Authors Guyton KZ, Chiu WA, Bateson TF, Jinot J, Scott CS, Brown RC, Caldwell JC
Title A reexamination of the PPAR-alpha activation mode of action as a basis for assessing human cancer risks of environmental contaminants.
Journal Related pleu00980 Metabolism of xenobiotics by cytochrome P450
pleu05204 Chemical carcinogenesis - DNA adducts
pleu05208 Chemical carcinogenesis - reactive oxygen species
KO pathway
