KEGG   PATHWAY: ptg05224
Entry
ptg05224                    Pathway                                
Name
Breast cancer - Panthera tigris altaica (Amur tiger)
Description
Breast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gland. The molecular subtypes of breast cancer, which are based on the presence or absence of hormone receptors (estrogen and progesterone subtypes) and human epidermal growth factor receptor-2 (HER2), include: hormone receptor positive and HER2 negative (luminal A subtype), hormone receptor positive and HER2 positive (luminal B subtype), hormone receptor negative and HER2 positive (HER2 positive), and hormone receptor negative and HER2 negative (basal-like or triple-negative breast cancers (TNBCs)). Hormone receptor positive breast cancers are largely driven by the estrogen/ER pathway. In HER2 positive breast tumours, HER2 activates the PI3K/AKT and the RAS/RAF/MAPK pathways, and stimulate cell growth, survival and differentiation. In patients suffering from TNBC, the deregulation of various signalling pathways (Notch and Wnt/beta-catenin), EGFR protein have been confirmed. In the case of breast cancer only 8% of all cancers are hereditary, a phenomenon linked to genetic changes in BRCA1 or BRCA2. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers.
Class
Human Diseases; Cancer: specific types
Pathway map
ptg05224  Breast cancer
ptg05224

Organism
Panthera tigris altaica (Amur tiger) [GN:ptg]
Gene
102969728  ESR1; estrogen receptor 1 [KO:K08550]
102972623  ESR2; estrogen receptor 2 [KO:K08551]
102950417  NCOA1; nuclear receptor coactivator 1 [KO:K09101] [EC:2.3.1.48]
102961259  NCOA3; nuclear receptor coactivator 3 [KO:K11256] [EC:2.3.1.48]
102952769  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
102958666  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102955984  SP1; Sp1 transcription factor [KO:K04684]
102959906  CCND1; cyclin D1 [KO:K04503]
102954147  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
102971231  PGR; progesterone receptor [KO:K08556]
102962277  WNT1; Wnt family member 1 [KO:K03209]
102954463  TNFSF11; tumor necrosis factor superfamily member 11 [KO:K05473]
102961961  ERBB2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
102967663  FGF1; fibroblast growth factor 1 [KO:K18496]
102969772  FGF2; fibroblast growth factor 2 [KO:K18497]
102970275  FGF9; fibroblast growth factor 9 [KO:K04358]
102949835  FGF5; fibroblast growth factor 5 [KO:K04358]
102971941  FGF22; fibroblast growth factor 22 [KO:K04358]
102964398  FGF18; fibroblast growth factor 18 [KO:K04358]
102959014  FGF8; fibroblast growth factor 8 [KO:K04358]
102956185  FGF7; fibroblast growth factor 7 [KO:K04358]
102970087  FGF17; fibroblast growth factor 17 [KO:K04358]
102957299  FGF20; fibroblast growth factor 20 [KO:K04358]
102970576  FGF10; fibroblast growth factor 10 [KO:K04358]
102969970  FGF6; fibroblast growth factor 6 [KO:K04358]
102966317  FGF19; fibroblast growth factor 19 [KO:K22603]
102963142  FGF21; fibroblast growth factor 21 [KO:K22429]
102958480  FGF23; fibroblast growth factor 23 [KO:K22428]
102972346  FGFR1; fibroblast growth factor receptor 1 [KO:K04362] [EC:2.7.10.1]
102962543  IGF1; insulin like growth factor 1 [KO:K05459]
102949680  IGF1R; insulin like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
102959656  EGF; epidermal growth factor [KO:K04357]
102967370  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102960767  KIT; KIT proto-oncogene receptor tyrosine kinase [KO:K05091] [EC:2.7.10.1]
102949026  SHC1; SHC adaptor protein 1 [KO:K06279]
102954336  SHC2; SHC adaptor protein 2 [KO:K17447]
102965813  SHC3; SHC adaptor protein 3 [KO:K17448]
102955115  SHC4; SHC adaptor protein 4 [KO:K17449]
102970459  GRB2; growth factor receptor bound protein 2 [KO:K04364]
102949403  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
102950748  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
102952119  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102957350  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102952980  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102956086  ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
102951082  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
102955852  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102969757  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102956808  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102964841  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102960964  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102953082  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102965070  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
102972487  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102949853  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102952993  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102967709  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102972446  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
102952603  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102954757  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102967196  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
102950850  RPS6KB2; ribosomal protein S6 kinase B2 [KO:K04688] [EC:2.7.11.1]
102960736  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
102963021  JAG1; jagged 1 [KO:K06052]
102961766  DLL4; delta like canonical Notch ligand 4 [KO:K06051]
102952034  DLL3; delta like canonical Notch ligand 3 [KO:K06051]
102951103  DLL1; delta like canonical Notch ligand 1 [KO:K06051]
102961729  NOTCH2; notch 2 [KO:K20994]
102953716  NOTCH3; notch 3 [KO:K20995]
102970846  NOTCH4; notch 4 [KO:K20996]
102955935  HES1; hes family bHLH transcription factor 1 [KO:K06054]
102959515  HEY1; hes related family bHLH transcription factor with YRPW motif 1 [KO:K09091]
102965569  HEYL; hes related family bHLH transcription factor with YRPW motif-like [KO:K09091]
102962900  HEY2; hes related family bHLH transcription factor with YRPW motif 2 [KO:K09091]
102960922  FLT4; fms related tyrosine kinase 4 [KO:K05097] [EC:2.7.10.1]
102964051  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
102960153  NFKB2; nuclear factor kappa B subunit 2 [KO:K04469]
102963336  WNT2B; Wnt family member 2B [KO:K00182]
102954954  WNT2; Wnt family member 2 [KO:K00182]
102950040  WNT3A; Wnt family member 3A [KO:K00312]
102962551  WNT3; Wnt family member 3 [KO:K00312]
102965201  WNT5A; Wnt family member 5A [KO:K00444]
102958778  WNT5B; Wnt family member 5B [KO:K00444]
102972888  WNT7A; Wnt family member 7A [KO:K00572]
102966525  WNT8A; Wnt family member 8A [KO:K00714]
102956179  WNT8B; Wnt family member 8B [KO:K00714]
102950323  WNT9A; Wnt family member 9A [KO:K01064]
102962257  WNT9B; Wnt family member 9B [KO:K01064]
102961987  WNT10B; Wnt family member 10B [KO:K01357]
102956294  WNT10A; Wnt family member 10A [KO:K01357]
102971675  WNT11; Wnt family member 11 [KO:K01384]
102959880  WNT16; Wnt family member 16 [KO:K01558]
102968815  FZD1; frizzled class receptor 1 [KO:K02432]
102948653  FZD7; frizzled class receptor 7 [KO:K02432]
102962395  FZD2; frizzled class receptor 2 [KO:K02235]
102961371  FZD3; frizzled class receptor 3 [KO:K02329]
102952336  FZD4; frizzled class receptor 4 [KO:K02354]
102953646  FZD6; frizzled class receptor 6 [KO:K02376]
102970273  FZD9; frizzled class receptor 9 [KO:K02842]
102953438  FZD10; frizzled class receptor 10 [KO:K02842]
102968327  LRP5; LDL receptor related protein 5 [KO:K03068]
102968142  LRP6; LDL receptor related protein 6 [KO:K03068]
102954084  DVL3; dishevelled segment polarity protein 3 [KO:K02353]
102967723  DVL2; dishevelled segment polarity protein 2 [KO:K02353]
102957003  DVL1; dishevelled segment polarity protein 1 [KO:K02353]
102961382  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
102951323  AXIN1; axin 1 [KO:K02157]
102967280  AXIN2; axin 2 [KO:K04385]
102948725  APC; APC, WNT signaling pathway regulator [KO:K02085]
102959570  CTNNB1; catenin beta 1 [KO:K02105]
102949834  CSNK1A1; casein kinase 1 alpha 1 [KO:K08957] [EC:2.7.11.1]
102957988  TCF7; transcription factor 7 (T-cell specific, HMG-box) [KO:K02620]
102958078  TCF7L1; transcription factor 7 like 1 [KO:K04490]
102961321  TCF7L2; transcription factor 7 like 2 [KO:K04491]
102970026  LEF1; lymphoid enhancer binding factor 1 [KO:K04492]
102962571  TP53; tumor protein p53 [KO:K04451]
102964763  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
102951885  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
102949153  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
102970767  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
102961097  DDB2; damage specific DNA binding protein 2 [KO:K10140]
102962803  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
102970281  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102967948  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102952365  RB1; RB transcriptional corepressor 1 [KO:K06618]
102963506  E2F1; E2F transcription factor 1 [KO:K17454]
102952251  E2F2; E2F transcription factor 2 [KO:K09389]
102948948  E2F3; E2F transcription factor 3 [KO:K06620]
102966376  BRCA1; BRCA1, DNA repair associated [KO:K10605] [EC:2.3.2.27]
102965865  BRCA2; BRCA2, DNA repair associated [KO:K08775]
Compound
C00410  Progesterone
C00951  Estradiol-17beta
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:24649067
  Authors
Zhang MH, Man HT, Zhao XD, Dong N, Ma SL
  Title
Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials (Review).
  Journal
Biomed Rep 2:41-52 (2014)
DOI:10.3892/br.2013.187
Reference
PMID:27390604
  Authors
Dai X, Xiang L, Li T, Bai Z
  Title
Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes.
  Journal
J Cancer 7:1281-94 (2016)
DOI:10.7150/jca.13141
Reference
PMID:20436504
  Authors
Schnitt SJ
  Title
Classification and prognosis of invasive breast cancer: from morphology to molecular taxonomy.
  Journal
Mod Pathol 23 Suppl 2:S60-4 (2010)
DOI:10.1038/modpathol.2010.33
Reference
PMID:23000897
  Authors
  Title
Comprehensive molecular portraits of human breast tumours.
  Journal
Nature 490:61-70 (2012)
DOI:10.1038/nature11412
Reference
PMID:22178455
  Authors
Eroles P, Bosch A, Perez-Fidalgo JA, Lluch A
  Title
Molecular biology in breast cancer: intrinsic subtypes and signaling pathways.
  Journal
Cancer Treat Rev 38:698-707 (2012)
DOI:10.1016/j.ctrv.2011.11.005
Reference
  Authors
Karamouzis MV, Papavassiliou KA, Adamopoulos C, Papavassiliou AG.
  Title
Targeting androgen/estrogen receptors crosstalk in cancer
  Journal
Trends Cancer 2:35-48 (2016)
DOI:10.1016/j.trecan.2015.12.001
Reference
  Authors
Sharp A, Harper-Wynne C.
  Title
Treatment of advanced breast cancer (ABC): the expanding landscape of targeted therapies
  Journal
J Cancer Biol Res 2:1036 (2014)
Reference
PMID:24596345
  Authors
Byler S, Goldgar S, Heerboth S, Leary M, Housman G, Moulton K, Sarkar S
  Title
Genetic and epigenetic aspects of breast cancer progression and therapy.
  Journal
Anticancer Res 34:1071-7 (2014)
Reference
PMID:23988612
  Authors
Mohamed A, Krajewski K, Cakar B, Ma CX
  Title
Targeted therapy for breast cancer.
  Journal
Am J Pathol 183:1096-112 (2013)
DOI:10.1016/j.ajpath.2013.07.005
Reference
PMID:22722193
  Authors
Ellis MJ, Ding L, Shen D, Luo J, Suman VJ, Wallis JW, Van Tine BA, Hoog J, Goiffon RJ, Goldstein TC, Ng S, Lin L, Crowder R, Snider J, Ballman K, Weber J, Chen K, Koboldt DC, Kandoth C, Schierding WS, McMichael JF, Miller CA, Lu C, Harris CC, McLellan MD, Wendl MC, DeSchryver K, Allred DC, Esserman L, Unzeitig G, Margenthaler J, Babiera GV, Marcom PK, Guenther JM, Leitch M, Hunt K, Olson J, Tao Y, Maher CA, Fulton LL, Fulton RS, Harrison M, Oberkfell B, Du F, Demeter R, Vickery TL, Elhammali A, Piwnica-Worms H, McDonald S, Watson M, Dooling DJ, Ota D, Chang LW, Bose R, Ley TJ, Piwnica-Worms D, Stuart JM, Wilson RK, Mardis ER
  Title
Whole-genome analysis informs breast cancer response to aromatase inhibition.
  Journal
Nature 486:353-60 (2012)
DOI:10.1038/nature11143
Reference
PMID:25907219
  Authors
Ma CX, Reinert T, Chmielewska I, Ellis MJ
  Title
Mechanisms of aromatase inhibitor resistance.
  Journal
Nat Rev Cancer 15:261-75 (2015)
DOI:10.1038/nrc3920
Reference
PMID:16113099
  Authors
Butt AJ, McNeil CM, Musgrove EA, Sutherland RL
  Title
Downstream targets of growth factor and oestrogen signalling and endocrine resistance: the potential roles of c-Myc, cyclin D1 and cyclin E.
  Journal
Endocr Relat Cancer 12 Suppl 1:S47-59 (2005)
DOI:10.1677/erc.1.00993
Reference
PMID:24111892
  Authors
Dasgupta S, Lonard DM, O'Malley BW
  Title
Nuclear receptor coactivators: master regulators of human health and disease.
  Journal
Annu Rev Med 65:279-92 (2014)
DOI:10.1146/annurev-med-051812-145316
Reference
PMID:23702927
  Authors
Brisken C
  Title
Progesterone signalling in breast cancer: a neglected hormone coming into the limelight.
  Journal
Nat Rev Cancer 13:385-96 (2013)
DOI:10.1038/nrc3518
Reference
PMID:20087430
  Authors
Scarpin KM, Graham JD, Mote PA, Clarke CL
  Title
Progesterone action in human tissues: regulation by progesterone receptor (PR) isoform expression, nuclear positioning and coregulator expression.
  Journal
Nucl Recept Signal 7:e009 (2009)
DOI:10.1621/nrs.07009
Reference
PMID:24291072
  Authors
Knutson TP, Lange CA
  Title
Tracking progesterone receptor-mediated actions in breast cancer.
  Journal
Pharmacol Ther 142:114-25 (2014)
DOI:10.1016/j.pharmthera.2013.11.010
Reference
PMID:25544707
  Authors
Dittrich A, Gautrey H, Browell D, Tyson-Capper A
  Title
The HER2 Signaling Network in Breast Cancer--Like a Spider in its Web.
  Journal
J Mammary Gland Biol Neoplasia 19:253-70 (2014)
DOI:10.1007/s10911-014-9329-5
Reference
PMID:21965336
  Authors
Higgins MJ, Baselga J
  Title
Targeted therapies for breast cancer.
  Journal
J Clin Invest 121:3797-803 (2011)
DOI:10.1172/JCI57152
Reference
PMID:26028978
  Authors
Mukohara T
  Title
PI3K mutations in breast cancer: prognostic and therapeutic implications.
  Journal
Breast Cancer (Dove Med Press) 7:111-23 (2015)
DOI:10.2147/BCTT.S60696
Reference
PMID:19088017
  Authors
Schneider BP, Winer EP, Foulkes WD, Garber J, Perou CM, Richardson A, Sledge GW, Carey LA
  Title
Triple-negative breast cancer: risk factors to potential targets.
  Journal
Clin Cancer Res 14:8010-8 (2008)
DOI:10.1158/1078-0432.CCR-08-1208
Reference
PMID:21898546
  Authors
King TD, Suto MJ, Li Y
  Title
The Wnt/beta-catenin signaling pathway: a potential therapeutic target in the treatment of triple negative breast cancer.
  Journal
J Cell Biochem 113:13-8 (2012)
DOI:10.1002/jcb.23350
Reference
PMID:11737884
  Authors
Brown AM
  Title
Wnt signaling in breast cancer: have we come full circle?
  Journal
Breast Cancer Res 3:351-5 (2001)
DOI:10.1186/bcr321
Reference
PMID:21076461
  Authors
Geyer FC, Lacroix-Triki M, Savage K, Arnedos M, Lambros MB, MacKay A, Natrajan R, Reis-Filho JS
  Title
beta-Catenin pathway activation in breast cancer is associated with triple-negative phenotype but not with CTNNB1 mutation.
  Journal
Mod Pathol 24:209-31 (2011)
DOI:10.1038/modpathol.2010.205
Reference
PMID:20971825
  Authors
Al-Hussaini H, Subramanyam D, Reedijk M, Sridhar SS
  Title
Notch signaling pathway as a therapeutic target in breast cancer.
  Journal
Mol Cancer Ther 10:9-15 (2011)
DOI:10.1158/1535-7163.MCT-10-0677
Reference
PMID:26968398
  Authors
Rangel MC, Bertolette D, Castro NP, Klauzinska M, Cuttitta F, Salomon DS
  Title
Developmental signaling pathways regulating mammary stem cells and contributing to the etiology of triple-negative breast cancer.
  Journal
Breast Cancer Res Treat 156:211-26 (2016)
DOI:10.1007/s10549-016-3746-7
Reference
PMID:26040571
  Authors
Jamdade VS, Sethi N, Mundhe NA, Kumar P, Lahkar M, Sinha N
  Title
Therapeutic targets of triple-negative breast cancer: a review.
  Journal
Br J Pharmacol 172:4228-37 (2015)
DOI:10.1111/bph.13211
Reference
PMID:23196196
  Authors
Karamboulas C, Ailles L
  Title
Developmental signaling pathways in cancer stem cells of solid tumors.
  Journal
Biochim Biophys Acta 1830:2481-95 (2013)
DOI:10.1016/j.bbagen.2012.11.008
Reference
PMID:23881035
  Authors
Ignatiadis M, Sotiriou C
  Title
Luminal breast cancer: from biology to treatment.
  Journal
Nat Rev Clin Oncol 10:494-506 (2013)
DOI:10.1038/nrclinonc.2013.124
Reference
PMID:25013431
  Authors
Shin SJ, Gong G, Lee HJ, Kang J, Bae YK, Lee A, Cho EY, Lee JS, Suh KS, Lee DW, Jung WH
  Title
Positive expression of insulin-like growth factor-1 receptor is associated with a positive hormone receptor status and a favorable prognosis in breast cancer.
  Journal
J Breast Cancer 17:113-20 (2014)
DOI:10.4048/jbc.2014.17.2.113
Reference
PMID:11879567
  Authors
Gasco M, Shami S, Crook T
  Title
The p53 pathway in breast cancer.
  Journal
Breast Cancer Res 4:70-6 (2002)
DOI:10.1186/bcr426
Reference
PMID:15343273
  Authors
Narod SA, Foulkes WD
  Title
BRCA1 and BRCA2: 1994 and beyond.
  Journal
Nat Rev Cancer 4:665-76 (2004)
DOI:10.1038/nrc1431
Related
pathway
ptg03440  Homologous recombination
ptg04010  MAPK signaling pathway
ptg04110  Cell cycle
ptg04115  p53 signaling pathway
ptg04151  PI3K-Akt signaling pathway
ptg04310  Wnt signaling pathway
ptg04330  Notch signaling pathway
ptg04915  Estrogen signaling pathway
KO pathway
ko05224   
LinkDB

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