KEGG   PATHWAY: hsa05213
Entry
hsa05213                    Pathway                                
Name
Endometrial cancer - Homo sapiens (human)
Description
Endometrial cancer (EC) is the most common gynaecological malignancy and the fourth most common malignancy in women in the developed world after breast, colorectal and lung cancer. Two types of endometrial carcinoma are distinguished with respect to biology and clinical course. Type-I carcinoma is related to hyperestrogenism by association with endometrial hyperplasia, frequent expression of estrogen and progesterone receptors and younger age, whereas type-II carcinoma is unrelated to estrogen, associated with atrophic endometrium, frequent lack of estrogen and progesterone receptors and older age. The morphologic differences in these cancers are mirrored in their molecular genetic profile with type I showing defects in DNA-mismatch repair and mutations in PTEN, K-ras, and beta-catenin, and type II showing aneuploidy, p53 mutations, and her2/neu amplification.
Class
Human Diseases; Cancer: specific types
Pathway map
hsa05213  Endometrial cancer
hsa05213

Network
  Element
N00012  Mutation-activated KRAS/NRAS to ERK signaling pathway
N00052  Mutation-inactivated PTEN to PI3K signaling pathway
N00058  Mutation-activated CTNNB1 to Wnt signaling pathway
N00115  Mutation-inactivated TP53 to transcription
Disease
H00026  Endometrial cancer
Organism
Homo sapiens (human) [GN:hsa]
Gene
1950  EGF; epidermal growth factor [KO:K04357]
1956  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
5290  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5295  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
5296  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
110117499  P3R3URF-PIK3R3; P3R3URF-PIK3R3 readthrough [KO:K02649]
5728  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
5170  PDPK1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
3611  ILK; integrin linked kinase [KO:K06272] [EC:2.7.11.1]
207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
842  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
572  BAD; BCL2 associated agonist of cell death [KO:K02158]
2309  FOXO3; forkhead box O3 [KO:K09408]
2885  GRB2; growth factor receptor bound protein 2 [KO:K04364]
6654  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
6655  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
3265  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
3845  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
4893  NRAS; NRAS proto-oncogene, GTPase [KO:K07828]
369  ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
673  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
5894  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
2002  ELK1; ETS transcription factor ELK1 [KO:K04375]
4292  MLH1; mutL homolog 1 [KO:K08734]
999  CDH1; cadherin 1 [KO:K05689]
1499  CTNNB1; catenin beta 1 [KO:K02105]
29119  CTNNA3; catenin alpha 3 [KO:K05691]
1495  CTNNA1; catenin alpha 1 [KO:K05691]
1496  CTNNA2; catenin alpha 2 [KO:K05691]
8312  AXIN1; axin 1 [KO:K02157]
8313  AXIN2; axin 2 [KO:K04385]
324  APC; APC regulator of WNT signaling pathway [KO:K02085]
10297  APC2; APC regulator of WNT signaling pathway 2 [KO:K02085]
2932  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
6932  TCF7; transcription factor 7 [KO:K02620]
83439  TCF7L1; transcription factor 7 like 1 [KO:K04490]
6934  TCF7L2; transcription factor 7 like 2 [KO:K04491]
51176  LEF1; lymphoid enhancer binding factor 1 [KO:K04492]
4609  MYC; MYC proto-oncogene, bHLH transcription factor [KO:K04377]
595  CCND1; cyclin D1 [KO:K04503]
7157  TP53; tumor protein p53 [KO:K04451]
1026  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
1647  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
4616  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
10912  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
581  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
578  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
1643  DDB2; damage specific DNA binding protein 2 [KO:K10140]
51426  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
2064  ERBB2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
Compound
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:15947972
  Authors
Ryan AJ, Susil B, Jobling TW, Oehler MK.
  Title
Endometrial cancer.
  Journal
Cell Tissue Res 322:53-61 (2005)
DOI:10.1007/s00441-005-1109-5
Reference
PMID:14747944
  Authors
Lax SF.
  Title
Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification.
  Journal
Virchows Arch 444:213-23 (2004)
DOI:10.1007/s00428-003-0947-3
Reference
PMID:16508724
  Authors
Shiozawa T, Konishi I.
  Title
Early endometrial carcinoma: clinicopathology, hormonal aspects, molecular genetics, diagnosis, and treatment.
  Journal
Int J Clin Oncol 11:13-21 (2006)
DOI:10.1007/s10147-005-0546-1
Reference
PMID:17028294
  Authors
Hecht JL, Mutter GL.
  Title
Molecular and pathologic aspects of endometrial carcinogenesis.
  Journal
J Clin Oncol 24:4783-91 (2006)
DOI:10.1200/JCO.2006.06.7173
Reference
PMID:11431710
  Authors
Matias-Guiu X, Catasus L, Bussaglia E, Lagarda H, Garcia A, Pons C, Munoz J, Arguelles R, Machin P, Prat J.
  Title
Molecular pathology of endometrial hyperplasia and carcinoma.
  Journal
Hum Pathol 32:569-77 (2001)
DOI:10.1053/hupa.2001.25929
Reference
PMID:15284264
  Authors
Slomovitz BM, Broaddus RR, Burke TW, Sneige N, Soliman PT, Wu W, Sun CC, Munsell MF, Gershenson DM, Lu KH.
  Title
Her-2/neu overexpression and amplification in uterine papillary serous carcinoma.
  Journal
J Clin Oncol 22:3126-32 (2004)
DOI:10.1200/JCO.2004.11.154
Reference
PMID:7585656
  Authors
Saffari B, Jones LA, el-Naggar A, Felix JC, George J, Press MF.
  Title
Amplification and overexpression of HER-2/neu (c-erbB2) in endometrial cancers: correlation with overall survival.
  Journal
Cancer Res 55:5693-8 (1995)
Reference
PMID:16248975
  Authors
Kim D, Chung J.
  Title
Akt: versatile mediator of cell survival and beyond.
  Journal
J Biochem Mol Biol 35:106-15 (2002)
DOI:10.5483/bmbrep.2002.35.1.106
Related
pathway
hsa04010  MAPK signaling pathway
hsa04012  ErbB signaling pathway
hsa04060  Cytokine-cytokine receptor interaction
hsa04110  Cell cycle
hsa04115  p53 signaling pathway
hsa04151  PI3K-Akt signaling pathway
hsa04310  Wnt signaling pathway
hsa04520  Adherens junction
KO pathway
ko05213   
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