KEGG   PATHWAY: oor05207
Entry
oor05207                    Pathway                                
Name
Chemical carcinogenesis - receptor activation - Orcinus orca (killer whale)
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: overview
Pathway map
oor05207  Chemical carcinogenesis - receptor activation
oor05207

Organism
Orcinus orca (killer whale) [GN:oor]
Gene
101280887  CHRNA7; neuronal acetylcholine receptor subunit alpha-7 [KO:K04809]
101280858  ARRB1; beta-arrestin-1 isoform X1 [KO:K04439]
125962100  ARRB2; beta-arrestin-2 isoform X1 [KO:K04439]
101275089  SRC; proto-oncogene tyrosine-protein kinase Src isoform X3 [KO:K05704] [EC:2.7.10.2]
101272984  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101272870  RB1; retinoblastoma-associated protein isoform X2 [KO:K06618]
101275686  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
101284595  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
101290359  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
101290416  CDC6; cell division control protein 6 homolog isoform X2 [KO:K02213]
101282274  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
101281369  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
101273673  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X4 [KO:K07211] [EC:2.7.11.10]
101273294  CCND1; G1/S-specific cyclin-D1 isoform X2 [KO:K04503]
101272643  CHRNA4; neuronal acetylcholine receptor subunit alpha-4 [KO:K04806]
101278948  CHRNB2; neuronal acetylcholine receptor subunit beta-2 [KO:K04813]
101277358  CHRNA3; neuronal acetylcholine receptor subunit alpha-3 [KO:K04805]
101277114  neuronal acetylcholine receptor subunit beta-4 [KO:K04815]
101272740  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X7 [KO:K04850]
101276749  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
101281199  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X11 [KO:K04853]
101275416  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
101272416  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B isoform X1 [KO:K04849]
101275783  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X1 [KO:K04344]
101278075  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101278974  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
101283011  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101277568  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101285437  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101281352  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X2 [KO:K02649]
101272095  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101288103  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101273316  AKT1; RAC-alpha serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101284249  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
101279857  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101270342  RELA; transcription factor p65 isoform X1 [KO:K04735]
101271947  GTPase HRas-like isoform X4 [KO:K02833]
101286301  HRAS; GTPase HRas isoform X2 [KO:K02833]
101281897  KRAS; GTPase KRas isoform X2 [KO:K07827]
101276138  NRAS; GTPase NRas [KO:K07828]
101286388  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101287162  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
101273287  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
101289394  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101286650  FOS; protein c-Fos [KO:K04379]
101288913  JUN; transcription factor Jun [KO:K04448]
101274490  MYC; myc proto-oncogene protein [KO:K04377]
101276750  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
101276350  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101277002  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101276418  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
101279969  VEGFA; vascular endothelial growth factor A isoform X3 [KO:K05448]
101280803  FGF2; fibroblast growth factor 2 [KO:K18497]
101286166  ADRB1; beta-1 adrenergic receptor [KO:K04141]
101276872  ADRB2; beta-2 adrenergic receptor [KO:K04142]
101283051  ADRB3; LOW QUALITY PROTEIN: beta-3 adrenergic receptor [KO:K04143]
101286834  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X2 [KO:K04632]
101282939  neuroendocrine secretory protein 55-like [KO:K04632]
101278368  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
101286207  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101283651  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
101289858  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
101283178  ADCY5; adenylate cyclase type 5 isoform X2 [KO:K08045] [EC:4.6.1.1]
101273023  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
101273592  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
101273171  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101281654  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101272376  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101273911  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101287685  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X2 [KO:K05870]
101276923  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X2 [KO:K04450]
101283438  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101283835  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
101286338  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X3 [KO:K09048]
101272184  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
101284966  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101287411  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X2 [KO:K09048]
101289047  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X4 [KO:K09047]
101273605  ATF6B; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
101276500  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
101277471  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
101271719  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101274967  BAD; bcl2-associated agonist of cell death [KO:K02158]
101285581  CHRNA9; neuronal acetylcholine receptor subunit alpha-9 isoform X2 [KO:K04810]
101276233  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X2 [KO:K04373] [EC:2.7.11.1]
101270674  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X2 [KO:K04373] [EC:2.7.11.1]
101287577  RPS6KA6; ribosomal protein S6 kinase alpha-6 isoform X2 [KO:K04373] [EC:2.7.11.1]
101273796  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X2 [KO:K04373] [EC:2.7.11.1]
101279259  ESR1; estrogen receptor [KO:K08550]
101274792  ESR2; estrogen receptor beta isoform X1 [KO:K08551]
101277927  VDR; vitamin D3 receptor isoform X3 [KO:K08539]
101274576  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
101275398  EGFR; epidermal growth factor receptor isoform X2 [KO:K04361] [EC:2.7.10.1]
101271441  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
101286587  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
105748221  LOW QUALITY PROTEIN: son of sevenless homolog 2-like [KO:K03099]
101284580  SOS2; son of sevenless homolog 2 isoform X2 [KO:K03099]
101277165  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
101286642  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X2 [KO:K04688] [EC:2.7.11.1]
101283084  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
101282132  PAQR7; membrane progestin receptor alpha isoform X2 [KO:K25039]
101273181  PAQR8; membrane progestin receptor beta isoform X6 [KO:K25040]
101271445  PAQR5; membrane progestin receptor gamma isoform X2 [KO:K25041]
101273743  PGR; progesterone receptor isoform X1 [KO:K08556]
101284929  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
101280792  STAT5A; signal transducer and activator of transcription 5A isoform X1 [KO:K11223]
101280265  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
101286728  BCL6; B-cell lymphoma 6 protein [KO:K15618]
101274941  KLF5; Krueppel-like factor 5 [KO:K09206]
101276094  KLF4; Krueppel-like factor 4 isoform X1 [KO:K17846]
101270541  WNT1; proto-oncogene Wnt-1 [KO:K03209]
101285038  NOTCH2; neurogenic locus notch homolog protein 2 isoform X1 [KO:K20994]
101273647  JAG1; protein jagged-1 isoform X1 [KO:K06052]
101273645  AR; androgen receptor isoform X1 [KO:K08557]
101283152  EGF; pro-epidermal growth factor [KO:K04357]
101287893  FGF17; fibroblast growth factor 17 [KO:K04358]
101273794  FGF4; fibroblast growth factor 4 [KO:K04358]
101274052  FGF3; LOW QUALITY PROTEIN: fibroblast growth factor 3 [KO:K04358]
101284280  FGF9; fibroblast growth factor 9 [KO:K04358]
101288260  FGF7; fibroblast growth factor 7 [KO:K04358]
101273136  FGF20; fibroblast growth factor 20 [KO:K04358]
101287969  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
101281389  FGF10; fibroblast growth factor 10 [KO:K04358]
101274700  FGF16; fibroblast growth factor 16 [KO:K04358]
101281106  FGF5; fibroblast growth factor 5 [KO:K04358]
101275198  FGF6; fibroblast growth factor 6 [KO:K04358]
101279631  FGF22; LOW QUALITY PROTEIN: fibroblast growth factor 22 [KO:K04358]
101276595  FGF18; fibroblast growth factor 18 [KO:K04358]
101279638  DLL3; delta-like protein 3 [KO:K06051]
101270732  DLL1; delta-like protein 1 [KO:K06051]
101275938  DLL4; delta-like protein 4 [KO:K06051]
101279225  PTGES3; prostaglandin E synthase 3 isoform X2 [KO:K15730] [EC:5.3.99.3]
101288246  AIP; AH receptor-interacting protein isoform X2 [KO:K17767]
101290282  AIPL1; aryl-hydrocarbon-interacting protein-like 1 isoform X2 [KO:K17767]
101288192  AHR; aryl hydrocarbon receptor [KO:K09093]
101285036  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
101278395  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
101271249  LOW QUALITY PROTEIN: heat shock protein HSP 90-beta-like [KO:K04079]
101289801  HSP90B1; endoplasmin [KO:K09487]
101269574  KPNA1; importin subunit alpha-5 [KO:K23940]
101286133  KPNA2; importin subunit alpha-1 [KO:K15043]
101272198  LOW QUALITY PROTEIN: importin subunit alpha-1-like [KO:K15043]
101289632  KPNA7; importin subunit alpha-8 [KO:K15043]
101269916  LOW QUALITY PROTEIN: importin subunit alpha-1-like [KO:K15043]
101285460  LOW QUALITY PROTEIN: importin subunit alpha-1-like [KO:K15043]
101276345  KPNA3; importin subunit alpha-4 isoform X1 [KO:K23583]
101280525  KPNA4; importin subunit alpha-3 isoform X2 [KO:K23583]
101273428  KPNA5; importin subunit alpha-6 [KO:K15042]
101273514  KPNA6; importin subunit alpha-7 isoform X3 [KO:K15042]
101274069  KPNB1; importin subunit beta-1 [KO:K14293]
101270436  ARNT; aryl hydrocarbon receptor nuclear translocator isoform X1 [KO:K09097]
101287158  cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]
101289532  cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1]
101288139  EPHX1; epoxide hydrolase 1 isoform X4 [KO:K01253] [EC:3.3.2.9]
101282222  EPHX2; bifunctional epoxide hydrolase 2 isoform X1 [KO:K08726] [EC:3.3.2.10 3.1.3.76]
101277852  EPHX3; epoxide hydrolase 3 [KO:K22368] [EC:3.3.2.10]
101289761  EPHX4; epoxide hydrolase 4 [KO:K22369] [EC:3.3.-.-]
105747731  glutathione S-transferase theta-4 [KO:K00799] [EC:2.5.1.18]
101290313  LOW QUALITY PROTEIN: glutathione S-transferase theta-1-like [KO:K00799] [EC:2.5.1.18]
101290060  glutathione S-transferase theta-2 [KO:K00799] [EC:2.5.1.18]
101269237  glutathione S-transferase theta-3-like isoform X2 [KO:K00799] [EC:2.5.1.18]
101289923  MGST3; microsomal glutathione S-transferase 3 [KO:K00799] [EC:2.5.1.18]
101276413  glutathione S-transferase omega-2 [KO:K00799] [EC:2.5.1.18]
101276819  GSTO1; glutathione S-transferase omega-1 isoform X3 [KO:K00799] [EC:2.5.1.18]
101282613  MGST2; microsomal glutathione S-transferase 2 [KO:K00799] [EC:2.5.1.18]
101274170  glutathione S-transferase A2 isoform X1 [KO:K00799] [EC:2.5.1.18]
101274411  GSTA4; glutathione S-transferase A4 isoform X1 [KO:K00799] [EC:2.5.1.18]
101278682  glutathione S-transferase Mu 3 [KO:K00799] [EC:2.5.1.18]
101280014  MGST1; microsomal glutathione S-transferase 1 isoform X1 [KO:K00799] [EC:2.5.1.18]
101277301  UDP-glucuronosyltransferase 1A1 isoform X1 [KO:K00699] [EC:2.4.1.17]
101274822  UDP-glucuronosyltransferase 2C1 isoform X1 [KO:K00699] [EC:2.4.1.17]
101276329  LOW QUALITY PROTEIN: UDP-glucuronosyltransferase 2A2 [KO:K00699] [EC:2.4.1.17]
101276585  LOW QUALITY PROTEIN: UDP-glucuronosyltransferase 2B4-like [KO:K00699] [EC:2.4.1.17]
101276904  NR1I3; LOW QUALITY PROTEIN: nuclear receptor subfamily 1 group I member 3 [KO:K08541]
101270600  RXRA; retinoic acid receptor RXR-alpha isoform X4 [KO:K08524]
101287304  RXRB; retinoic acid receptor RXR-beta isoform X4 [KO:K08525]
101289285  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
117200989  cytochrome P450 3A28-like isoform X1 [KO:K07424] [EC:1.14.14.1]
101287407  cytochrome P450 1A2 isoform X1 [KO:K07409] [EC:1.14.14.1]
101283267  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
Compound
C00076  Calcium cation
C00410  Progesterone
C00547  L-Noradrenaline
C00575  3',5'-Cyclic AMP
C00745  Nicotine
C00780  Serotonin
C00788  L-Adrenaline
C00951  Estradiol-17beta
C03690  Bis(2-ethylhexyl)phthalate
C04623  DDT
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C06697  Arsenite
C06790  Trichloroethene
C06916  Clofibrate
C07020  Gemfibrozil
C07434  Phenobarbital
C07535  Benzo[a]pyrene
C07557  2,3,7,8-Tetrachlorodibenzodioxin
C08150  Medroxyprogesterone acetate
C11042  Hexachlorobenzene
C11150  Trichloroacetate
C11371  Nafenopin
C11906  Sodium arsenite
C13624  Bisphenol A
C14240  Di(2-ethylhexyl) adipate
C14573  3,3',4,4',5-Pentachlorobiphenyl
C15995  Bombesin
C16452  N'-Nitrosonornicotine
C16453  4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone
Reference
PMID:15660110
  Authors
Luch A.
  Title
Nature and nurture - lessons from chemical carcinogenesis.
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Nat Rev Cancer 5:113-25 (2005)
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Reference
PMID:19631282
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Mutat Res 682:94-109 (2009)
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Reference
PMID:21444681
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Wu CH, Lee CH, Ho YS
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Nicotinic acetylcholine receptor-based blockade: applications of molecular targets for cancer therapy.
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Clin Cancer Res 17:3533-41 (2011)
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Reference
PMID:19194381
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Is cancer triggered by altered signalling of nicotinic acetylcholine receptors?
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Nat Rev Cancer 9:195-205 (2009)
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Reference
PMID:21541211
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Singh S, Pillai S, Chellappan S
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Nicotinic acetylcholine receptor signaling in tumor growth and metastasis.
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J Oncol 2011:456743 (2011)
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Reference
PMID:31956359
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Cheng WL, Chen KY, Lee KY, Feng PH, Wu SM
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Nicotinic-nAChR signaling mediates drug resistance in lung cancer.
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J Cancer 11:1125-1140 (2020)
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Reference
PMID:24827506
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Connections of nicotine to cancer.
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Nat Rev Cancer 14:419-29 (2014)
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Reference
PMID:24398389
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Schaal C, Chellappan SP
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Mol Cancer Res 12:14-23 (2014)
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PMID:21640716
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Nicotinic acetylcholine receptor-mediated mechanisms in lung cancer.
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Biochem Pharmacol 82:1015-21 (2011)
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Reference
PMID:18262664
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Nicotinic acetylcholine receptors in cancer: multiple roles in proliferation and inhibition of apoptosis.
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Trends Pharmacol Sci 29:151-8 (2008)
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Mechanisms of Cancer Induction by Tobacco-Specific NNK and NNN.
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Cancers (Basel) 6:1138-56 (2014)
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Reference
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Lung carcinoma signaling pathways activated by smoking.
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Chin J Cancer 30:551-8 (2011)
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Reference
PMID:28664511
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The Role of Nitrosamine (NNK) in Breast Cancer Carcinogenesis.
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J Mammary Gland Biol Neoplasia 22:159-170 (2017)
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IKBKE is induced by STAT3 and tobacco carcinogen and determines chemosensitivity in non-small cell lung cancer.
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Oncogene 32:151-9 (2013)
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PMID:20106947
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Chen RJ, Ho YS, Guo HR, Wang YJ
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Toxicol Sci 115:118-30 (2010)
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PMID:20953833
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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
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Crosstalk between nicotine and estrogen-induced estrogen receptor activation induces alpha9-nicotinic acetylcholine receptor expression in human breast cancer cells.
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Breast Cancer Res Treat 129:331-45 (2011)
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N Engl J Med 354:270-82 (2006)
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Reference
PMID:29229539
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Bisphenol A (BPA) and cell signaling pathways.
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Biotechnol Adv 36:311-327 (2018)
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Reference
PMID:28251049
  Authors
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Low-Dose Bisphenol A Exposure: A Seemingly Instigating Carcinogenic Effect on Breast Cancer.
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Adv Sci (Weinh) 4:1600248 (2017)
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Carcinogenesis 38:252-260 (2017)
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PI3K/Akt/mTOR Signaling Pathway and the Biphasic Effect of Arsenic in Carcinogenesis.
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Cancers (Basel) 12:E2440 (2020)
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J Mammary Gland Biol Neoplasia 20:39-50 (2015)
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Related
pathway
oor00980  Metabolism of xenobiotics by cytochrome P450
oor03320  PPAR signaling pathway
oor04010  MAPK signaling pathway
oor04024  cAMP signaling pathway
oor04150  mTOR signaling pathway
oor04151  PI3K-Akt signaling pathway
oor04370  VEGF signaling pathway
oor04915  Estrogen signaling pathway
oor05204  Chemical carcinogenesis - DNA adducts
oor05206  MicroRNAs in cancer
oor05208  Chemical carcinogenesis - reactive oxygen species
KO pathway
ko05207   
LinkDB

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