KEGG   PATHWAY: epz05224
Entry
epz05224                    Pathway                                
Name
Breast cancer - Equus przewalskii (Przewalski's horse)
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
epz05224  Breast cancer
epz05224

Organism
Equus przewalskii (Przewalski's horse) [GN:epz]
Gene
103547564  ESR1; estrogen receptor 1 [KO:K08550]
103541749  estrogen receptor beta-like [KO:K08551]
103547826  NCOA1; nuclear receptor coactivator 1 [KO:K09101] [EC:2.3.1.48]
103557987  NCOA3; nuclear receptor coactivator 3 [KO:K11256] [EC:2.3.1.48]
103548618  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
103559402  SP1; Sp1 transcription factor [KO:K04684]
103567860  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
103562544  PGR; progesterone receptor [KO:K08556]
103552200  WNT1; Wnt family member 1 [KO:K03209]
103558485  WNT4; Wnt family member 4 [KO:K00408]
103560371  TNFSF11; tumor necrosis factor superfamily member 11 [KO:K05473]
103550160  ERBB2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
103550265  FGF1; fibroblast growth factor 1 [KO:K18496]
103542783  FGF18; fibroblast growth factor 18 [KO:K04358]
103549913  FGF5; fibroblast growth factor 5 [KO:K04358]
103551851  FGF7; fibroblast growth factor 7 [KO:K04358]
103551394  FGF8; fibroblast growth factor 8 [KO:K04358]
103568034  FGF17; fibroblast growth factor 17 [KO:K04358]
103542556  fibroblast growth factor 4-like [KO:K04358]
103556855  FGF20; fibroblast growth factor 20 [KO:K04358]
103557835  FGF6; fibroblast growth factor 6 [KO:K04358]
103558900  FGF9; fibroblast growth factor 9 [KO:K04358]
103544754  FGF22; fibroblast growth factor 22 [KO:K04358]
103559741  FGF10; fibroblast growth factor 10 [KO:K04358]
103544063  FGF3; fibroblast growth factor 3 [KO:K04358]
103543606  fibroblast growth factor 16 [KO:K04358]
103542877  FGF19; fibroblast growth factor 19 [KO:K22603]
103553325  FGF21; fibroblast growth factor 21 [KO:K22429]
103567716  FGF23; fibroblast growth factor 23 [KO:K22428]
103560266  FGFR1; fibroblast growth factor receptor 1 [KO:K04362] [EC:2.7.10.1]
103549360  IGF1; insulin like growth factor 1 [KO:K05459]
103559577  IGF1R; insulin like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
103543333  pro-epidermal growth factor-like [KO:K04357]
103560128  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
103554972  KIT; KIT proto-oncogene receptor tyrosine kinase [KO:K05091] [EC:2.7.10.1]
103552865  SHC1; SHC adaptor protein 1 [KO:K06279]
103542441  SHC2; SHC adaptor protein 2 [KO:K17447]
103552516  SHC3; SHC adaptor protein 3 [KO:K17448]
103551857  SHC4; SHC adaptor protein 4 [KO:K17449]
103546580  GRB2; growth factor receptor bound protein 2 [KO:K04364]
103553088  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
103556123  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
103567332  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
103546629  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
103552675  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103555338  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
103554541  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103549630  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103543290  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
103547261  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103562408  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103549076  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103554655  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform-like [KO:K00922] [EC:2.7.1.153]
103552150  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103548220  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103551868  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103561550  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103561454  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
103560497  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103540249  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103555421  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103552237  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
103565282  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
103559935  RPS6KB2; ribosomal protein S6 kinase B2 [KO:K04688] [EC:2.7.11.1]
103551777  JAG1; jagged 1 [KO:K06052]
103567391  JAG2; jagged 2 [KO:K21635]
103558860  DLL3; delta like canonical Notch ligand 3 [KO:K06051]
103556273  DLL1; delta like canonical Notch ligand 1 [KO:K06051]
103542262  DLL4; delta like canonical Notch ligand 4 [KO:K06051]
103565355  NOTCH1; notch 1 [KO:K02599]
103548385  NOTCH2; notch 2 [KO:K20994]
103544084  NOTCH3; notch 3 [KO:K20995]
103566651  NOTCH4; notch 4 [KO:K20996]
103560632  HES1; hes family bHLH transcription factor 1 [KO:K06054]
103568042  HEY2; hes related family bHLH transcription factor with YRPW motif 2 [KO:K09091]
103550826  HEY1; hes related family bHLH transcription factor with YRPW motif 1 [KO:K09091]
103564331  HEYL; hes related family bHLH transcription factor with YRPW motif-like [KO:K09091]
103566205  FLT4; fms related tyrosine kinase 4 [KO:K05097] [EC:2.7.10.1]
103564535  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
103558148  NFKB2; nuclear factor kappa B subunit 2 [KO:K04469]
103550603  WNT2; Wnt family member 2 [KO:K00182]
103541803  WNT2B; Wnt family member 2B [KO:K00182]
103552917  WNT3; Wnt family member 3 [KO:K00312]
103565876  WNT3A; Wnt family member 3A [KO:K00312]
103565849  WNT5A; Wnt family member 5A [KO:K00444]
103555816  WNT5B; Wnt family member 5B [KO:K00444]
103543266  protein Wnt-5b-like [KO:K00444]
103567913  WNT6; Wnt family member 6 [KO:K00445]
103556791  WNT7A; Wnt family member 7A [KO:K00572]
103558099  WNT7B; Wnt family member 7B [KO:K00572]
103563555  WNT8A; Wnt family member 8A [KO:K00714]
103562517  WNT8B; Wnt family member 8B [KO:K00714]
103554698  WNT9B; Wnt family member 9B [KO:K01064]
103565875  WNT9A; Wnt family member 9A [KO:K01064]
103552222  WNT10B; Wnt family member 10B [KO:K01357]
103567916  WNT10A; Wnt family member 10A [KO:K01357]
103548228  WNT11; Wnt family member 11 [KO:K01384]
103564131  WNT16; Wnt family member 16 [KO:K01558]
103560190  FZD1; frizzled class receptor 1 [KO:K02432]
103567476  FZD7; frizzled class receptor 7 [KO:K02432]
103551209  FZD2; frizzled class receptor 2 [KO:K02235]
103567492  FZD3; frizzled class receptor 3 [KO:K02329]
103564599  FZD4; frizzled class receptor 4 [KO:K02354]
103548916  FZD5; frizzled class receptor 5 [KO:K02375]
103565119  FZD6; frizzled class receptor 6 [KO:K02376]
103548763  FZD10; frizzled class receptor 10 [KO:K02842]
103566121  FZD9; frizzled class receptor 9 [KO:K02842]
103546713  LRP6; LDL receptor related protein 6 [KO:K03068]
103551283  LRP5; LDL receptor related protein 5 [KO:K03068]
103554749  DVL3; dishevelled segment polarity protein 3 [KO:K02353]
103557742  DVL2; dishevelled segment polarity protein 2 [KO:K02353]
103542807  DVL1; dishevelled segment polarity protein 1 [KO:K02353]
103547424  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
103564115  AXIN1; axin 1 [KO:K02157]
103553492  AXIN2; axin 2 [KO:K04385]
103561228  APC; APC, WNT signaling pathway regulator [KO:K02085]
103552888  CTNNB1; catenin beta 1 [KO:K02105]
103556289  CSNK1A1; casein kinase 1 alpha 1 [KO:K08957] [EC:2.7.11.1]
103543120  TCF7; transcription factor 7 (T-cell specific, HMG-box) [KO:K02620]
103548276  TCF7L1; transcription factor 7 like 1 [KO:K04490]
103564289  TCF7L2; transcription factor 7 like 2 [KO:K04491]
103557035  LEF1; lymphoid enhancer binding factor 1 [KO:K04492]
103557703  TP53; tumor protein p53 [KO:K04451]
103552106  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
103543986  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
103564848  growth arrest and DNA damage-inducible protein GADD45 alpha-like [KO:K04402]
103553312  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
103544222  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
103566732  DDB2; damage specific DNA binding protein 2 [KO:K10140]
103563108  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
103553644  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103549196  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
103549440  RB1; RB transcriptional corepressor 1 [KO:K06618]
103541516  E2F1; E2F transcription factor 1 [KO:K17454]
103551301  E2F2; E2F transcription factor 2 [KO:K09389]
103549781  E2F3; E2F transcription factor 3 [KO:K06620]
103566867  BRCA1; BRCA1, DNA repair associated [KO:K10605] [EC:2.3.2.27]
103543936  BRCA2; BRCA2, DNA repair associated [KO:K08775]
Compound
C00410  Progesterone
C00951  Estradiol-17beta
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  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
  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
  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
  Authors
  Title
Comprehensive molecular portraits of human breast tumours.
  Journal
Nature 490:61-70 (2012)
DOI:10.1038/nature11412
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  Authors
Higgins MJ, Baselga J
  Title
Targeted therapies for breast cancer.
  Journal
J Clin Invest 121:3797-803 (2011)
DOI:10.1172/JCI57152
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
epz03440  Homologous recombination
epz04010  MAPK signaling pathway
epz04110  Cell cycle
epz04115  p53 signaling pathway
epz04151  PI3K-Akt signaling pathway
epz04310  Wnt signaling pathway
epz04330  Notch signaling pathway
epz04915  Estrogen signaling pathway
KO pathway
ko05224   
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