KEGG   PATHWAY: hai05207
Entry
hai05207                    Pathway                                
Name
Chemical carcinogenesis - receptor activation - Hipposideros armiger (great roundleaf bat)
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
hai05207  Chemical carcinogenesis - receptor activation
hai05207

Organism
Hipposideros armiger (great roundleaf bat) [GN:hai]
Gene
109372169  neuronal acetylcholine receptor subunit alpha-7 isoform X1 [KO:K04809]
109394691  ARRB2; beta-arrestin-2 isoform X1 [KO:K04439]
109386336  ARRB1; beta-arrestin-1 isoform X1 [KO:K04439]
109377191  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
109384548  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
109387138  RB1; retinoblastoma-associated protein [KO:K06618]
109377242  E2F1; transcription factor E2F1 [KO:K17454]
109383622  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
109390892  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
109380808  CDC6; cell division control protein 6 homolog [KO:K02213]
109375294  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
109384506  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
109395763  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
109386512  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
109389297  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
109380068  CHRNA4; neuronal acetylcholine receptor subunit alpha-4 isoform X1 [KO:K04806]
109393402  CHRNB2; neuronal acetylcholine receptor subunit beta-2 [KO:K04813]
109381384  CHRNA3; neuronal acetylcholine receptor subunit alpha-3 [KO:K04805]
109381468  CHRNB4; neuronal acetylcholine receptor subunit beta-4 isoform X1 [KO:K04815]
109388950  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
109395944  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
109374806  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
109380439  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
109382541  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B [KO:K04849]
109394251  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X1 [KO:K04344]
109381238  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
109394108  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
109372681  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
109382484  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
109395865  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
109373811  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
109381083  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
109385878  RAC-beta serine/threonine-protein kinase-like isoform X1 [KO:K04456] [EC:2.7.11.1]
109374859  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
109385353  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
109381262  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
109372541  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
109384322  RELA; transcription factor p65 isoform X1 [KO:K04735]
109375639  HRAS; GTPase HRas isoform X1 [KO:K02833]
109385150  GTPase HRas-like [KO:K02833]
109389264  KRAS; GTPase KRas isoform X1 [KO:K07827]
109377015  NRAS; GTPase NRas [KO:K07828]
109385252  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
109388626  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
109385803  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
109394900  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109381526  FOS; proto-oncogene c-Fos [KO:K04379]
109371251  JUN; transcription factor AP-1 [KO:K04448]
109371257  transcription factor AP-1 [KO:K04448]
109383211  MYC; myc proto-oncogene protein [KO:K04377]
109390784  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
109380289  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
109386578  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
109372505  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
109382864  VEGFA; vascular endothelial growth factor A [KO:K05448]
109374154  FGF2; fibroblast growth factor 2 [KO:K18497]
109392029  ADRB1; beta-1 adrenergic receptor [KO:K04141]
109371751  ADRB2; beta-2 adrenergic receptor [KO:K04142]
109393585  ADRB3; beta-3 adrenergic receptor [KO:K04143]
109380071  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
109380072  neuroendocrine secretory protein 55 [KO:K04632]
109373011  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
109375976  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
109385186  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
109393593  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
109387200  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
109393238  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
109383261  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
109372359  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
109392133  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
109385440  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
109394225  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
109388316  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
109388738  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
109392248  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
109373471  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
109393756  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
109388532  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
109390233  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
109388636  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
109381368  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
109373089  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
109377665  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
109375288  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
109392892  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
109384256  BAD; bcl2-associated agonist of cell death [KO:K02158]
109381764  CHRNA9; neuronal acetylcholine receptor subunit alpha-9 [KO:K04810]
109395688  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X1 [KO:K04373] [EC:2.7.11.1]
109386772  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X1 [KO:K04373] [EC:2.7.11.1]
109373920  RPS6KA2; ribosomal protein S6 kinase alpha-2 [KO:K04373] [EC:2.7.11.1]
109380859  ESR1; estrogen receptor isoform X1 [KO:K08550]
109376252  ESR2; estrogen receptor beta isoform X1 [KO:K08551]
109372509  VDR; vitamin D3 receptor [KO:K08539]
109382891  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
109388365  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
109383688  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
109385471  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
109375221  SOS2; son of sevenless homolog 2 [KO:K03099]
109393572  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
109379764  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
109384219  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
109386785  PAQR7; membrane progestin receptor alpha isoform X1 [KO:K25039]
109391314  PAQR8; membrane progestin receptor beta [KO:K25040]
109385269  PAQR5; membrane progestin receptor gamma [KO:K25041]
109376738  PGR; progesterone receptor isoform X1 [KO:K08556]
109386844  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
109395760  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
109371168  BCL6; B-cell lymphoma 6 protein isoform X1 [KO:K15618]
109387907  KLF5; Krueppel-like factor 5 [KO:K09206]
109379268  KLF4; Krueppel-like factor 4 isoform X1 [KO:K17846]
109393219  WNT1; proto-oncogene Wnt-1 [KO:K03209]
109389880  NOTCH2; neurogenic locus notch homolog protein 2 [KO:K20994]
109378995  JAG1; protein jagged-1 [KO:K06052]
109385580  AR; androgen receptor [KO:K08557]
109379436  EGF; pro-epidermal growth factor [KO:K04357]
109379381  FGF18; fibroblast growth factor 18 [KO:K04358]
109379623  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
109394542  FGF7; fibroblast growth factor 7 [KO:K04358]
109382437  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
109385680  FGF16; fibroblast growth factor 16 [KO:K04358]
109389289  FGF3; fibroblast growth factor 3 [KO:K04358]
109389290  FGF4; fibroblast growth factor 4 [KO:K04358]
109394578  FGF20; fibroblast growth factor 20 [KO:K04358]
109373530  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
109392478  FGF6; fibroblast growth factor 6 [KO:K04358]
109392844  FGF10; fibroblast growth factor 10 [KO:K04358]
109377773  FGF9; fibroblast growth factor 9 isoform X1 [KO:K04358]
109390582  FGF22; fibroblast growth factor 22 [KO:K04358]
109383961  DLL4; delta-like protein 4 [KO:K06051]
109395346  DLL3; delta-like protein 3 [KO:K06051]
109391679  DLL1; delta-like protein 1 [KO:K06051]
109396906  PTGES3; prostaglandin E synthase 3 isoform X1 [KO:K15730] [EC:5.3.99.3]
109384246  AIP; AH receptor-interacting protein isoform X1 [KO:K17767]
109391873  AIPL1; aryl-hydrocarbon-interacting protein-like 1 isoform X1 [KO:K17767]
109386991  AHR; aryl hydrocarbon receptor [KO:K09093]
109381021  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
109382930  HSP90AB1; LOW QUALITY PROTEIN: heat shock protein HSP 90-beta [KO:K04079]
109387780  HSP90B1; endoplasmin [KO:K09487]
109388210  KPNA1; importin subunit alpha-5 [KO:K23940]
109380254  KPNA2; importin subunit alpha-1 [KO:K15043]
109389758  KPNA7; importin subunit alpha-8 [KO:K15043]
109373154  KPNA4; importin subunit alpha-3 isoform X1 [KO:K23583]
109387143  KPNA3; importin subunit alpha-4 isoform X1 [KO:K23583]
109391789  KPNA6; importin subunit alpha-7 isoform X1 [KO:K15042]
109396460  KPNA5; importin subunit alpha-6 isoform X1 [KO:K15042]
109380819  KPNB1; importin subunit beta-1 [KO:K14293]
109372278  ARNT; aryl hydrocarbon receptor nuclear translocator isoform X1 [KO:K09097]
109396247  cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]
109385488  cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1]
109391461  EPHX1; epoxide hydrolase 1 [KO:K01253] [EC:3.3.2.9]
109379561  EPHX2; bifunctional epoxide hydrolase 2 isoform X1 [KO:K08726] [EC:3.3.2.10 3.1.3.76]
109376078  EPHX3; epoxide hydrolase 3 isoform X1 [KO:K22368] [EC:3.3.2.10]
109373249  EPHX4; epoxide hydrolase 4 [KO:K22369] [EC:3.3.-.-]
109379590  glutathione S-transferase omega-2-like [KO:K00799] [EC:2.5.1.18]
109379616  GSTO1; glutathione S-transferase omega-1 [KO:K00799] [EC:2.5.1.18]
109385209  MGST3; microsomal glutathione S-transferase 3 [KO:K00799] [EC:2.5.1.18]
109371560  GSTM3; glutathione S-transferase Mu 3 [KO:K00799] [EC:2.5.1.18]
109394864  LOW QUALITY PROTEIN: glutathione S-transferase theta-2B-like [KO:K00799] [EC:2.5.1.18]
109394911  glutathione S-transferase theta-3-like isoform X1 [KO:K00799] [EC:2.5.1.18]
109394912  glutathione S-transferase theta-1 isoform X1 [KO:K00799] [EC:2.5.1.18]
109378801  glutathione S-transferase theta-3-like [KO:K00799] [EC:2.5.1.18]
109391304  glutathione S-transferase A3-like [KO:K00799] [EC:2.5.1.18]
109391315  GSTA4; glutathione S-transferase A4 [KO:K00799] [EC:2.5.1.18]
109383169  MGST1; microsomal glutathione S-transferase 1 [KO:K00799] [EC:2.5.1.18]
109394184  MGST2; microsomal glutathione S-transferase 2 isoform X1 [KO:K00799] [EC:2.5.1.18]
109391297  glutathione S-transferase alpha-4-like [KO:K00799] [EC:2.5.1.18]
109394880  glutathione S-transferase theta-4 [KO:K00799] [EC:2.5.1.18]
109375062  UDP-glucuronosyltransferase 1-1-like isoform X1 [KO:K00699] [EC:2.4.1.17]
109377020  UDP-glucuronosyltransferase 2A2 isoform X1 [KO:K00699] [EC:2.4.1.17]
109377021  UDP-glucuronosyltransferase 2A3-like [KO:K00699] [EC:2.4.1.17]
109376175  UDP-glucuronosyltransferase 2B31-like isoform X1 [KO:K00699] [EC:2.4.1.17]
109376177  UDP-glucuronosyltransferase 2B31-like [KO:K00699] [EC:2.4.1.17]
109376178  UDP-glucuronosyltransferase 2B31-like [KO:K00699] [EC:2.4.1.17]
109376179  UDP-glucuronosyltransferase 2B31-like [KO:K00699] [EC:2.4.1.17]
109376598  cytochrome P450 2B11-like [KO:K07412] [EC:1.14.14.1]
109376600  cytochrome P450 2B11-like [KO:K07412] [EC:1.14.14.1]
109376942  NR1I3; nuclear receptor subfamily 1 group I member 3 isoform X1 [KO:K08541]
109381229  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
109392460  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
109385199  retinoic acid receptor RXR-gamma-like isoform X1 [KO:K08526]
109392300  retinoic acid receptor RXR-gamma-like [KO:K08526]
109378053  cytochrome P450 3A12-like [KO:K07424] [EC:1.14.14.1]
109396253  cytochrome P450 1A2 isoform X1 [KO:K07409] [EC:1.14.14.1]
109387625  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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PMID:19631282
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Clin Cancer Res 17:3533-41 (2011)
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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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J Oncol 2011:456743 (2011)
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PMID:31956359
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Cheng WL, Chen KY, Lee KY, Feng PH, Wu SM
  Title
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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Grando SA
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Connections of nicotine to cancer.
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Nat Rev Cancer 14:419-29 (2014)
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PMID:24398389
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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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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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  Title
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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Gankhuyag N, Lee KH, Cho JY
  Title
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
  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.
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Toxicol Sci 115:118-30 (2010)
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Reference
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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Yager JD, Davidson NE
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Estrogen carcinogenesis in breast cancer.
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N Engl J Med 354:270-82 (2006)
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Reference
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Related
pathway
hai00980  Metabolism of xenobiotics by cytochrome P450
hai03320  PPAR signaling pathway
hai04010  MAPK signaling pathway
hai04024  cAMP signaling pathway
hai04150  mTOR signaling pathway
hai04151  PI3K-Akt signaling pathway
hai04370  VEGF signaling pathway
hai04915  Estrogen signaling pathway
hai05204  Chemical carcinogenesis - DNA adducts
hai05206  MicroRNAs in cancer
hai05208  Chemical carcinogenesis - reactive oxygen species
KO pathway
ko05207   
LinkDB

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