KEGG   PATHWAY: oas05219
oas05219                    Pathway                                

Bladder cancer - Ovis aries (sheep)
The urothelium covers the luminal surface of almost the entire urinary tract, extending from the renal pelvis, through the ureter and bladder, to the proximal urethra. The majority of urothelial carcinoma are bladder carcinomas, and urothelial carcinomas of the renal pelvis and ureter account for only approximately 7% of the total. Urothelial tumours arise and evolve through divergent phenotypic pathways. Some tumours progress from urothelial hyperplasia to low-grade non-invasive superficial papillary tumours. More aggressive variants arise either from flat, high-grade carcinoma in situ (CIS) and progress to invasive tumours, or they arise de novo as invasive tumours. Low-grade papillary tumors frequently show a constitutive activation of the receptor tyrosine kinase-Ras pathway, exhibiting activating mutations in the HRAS and fibroblast growth factor receptor 3 (FGFR3) genes. In contrast, CIS and invasive tumors frequently show alterations in the TP53 and RB genes and pathways. Invasion and metastases are promoted by several factors that alter the tumour microenvironment, including the aberrant expression of E-cadherins (E-cad), matrix metalloproteinases (MMPs), angiogenic factors such as vascular endothelial growth factor (VEGF).
Human Diseases; Cancer: specific types
Pathway map
oas05219  Bladder cancer

Ovis aries (sheep) [GN:oas]
554324  FGFR3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:]
101104357  HRAS; GTPase HRas isoform X1 [KO:K02833]
114114919  GTPase HRas-like [KO:K02833]
101114005  KRAS; GTPase KRas isoform X1 [KO:K07827]
101102438  NRAS; GTPase NRas [KO:K07828]
100305131  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:]
101107438  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:]
101103190  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:]
101123635  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:]
101113846  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:]
101115485  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
101123008  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
101115714  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X4 [KO:K04445] [EC:]
443447  MYC; myc proto-oncogene protein [KO:K04377]
100302080  RASSF1; ras association domain-containing protein 1 [KO:K09850]
101123304  DAPK2; death-associated protein kinase 2 isoform X1 [KO:K08803] [EC:]
101114352  DAPK3; death-associated protein kinase 3 [KO:K08803] [EC:]
101113985  DAPK1; death-associated protein kinase 1 isoform X1 [KO:K08803] [EC:]
114113021  cyclin-dependent kinase inhibitor 2A-like isoform X1 [KO:K06621]
101104979  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:]
101103187  E3 ubiquitin-protein ligase Mdm2-like [KO:K06643] [EC:]
443421  TP53; cellular tumor antigen p53 [KO:K04451]
100302083  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100144763  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100144756  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:]
100144755  RB1; retinoblastoma-associated protein [KO:K06618]
101117526  E2F1; transcription factor E2F1 [KO:K17454]
105606975  E2F2; transcription factor E2F2 [KO:K09389]
101121809  E2F3; transcription factor E2F3 [KO:K06620]
101106433  THBS1; thrombospondin-1 isoform X1 [KO:K16857]
101118185  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
443115  MMP2; 72 kDa type IV collagenase precursor [KO:K01398] [EC:]
100192422  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:]
101119631  UPK3A; uroplakin-3a isoform X1 [KO:K19520]
101103084  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:]
780519  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:]
780479  EGFR; epidermal growth factor receptor [KO:K04361] [EC:]
443103  VEGFA; vascular endothelial growth factor A precursor [KO:K05448]
101120355  MMP1; interstitial collagenase [KO:K01388] [EC:]
443418  CXCL8; interleukin-8 precursor [KO:K10030]
101119747  CDH1; cadherin-1 [KO:K05689]
Mitra AP, Datar RH, Cote RJ.
Molecular pathways in invasive bladder cancer: new insights into mechanisms, progression, and target identification.
J Clin Oncol 24:5552-64 (2006)
Wolff EM, Liang G, Jones PA.
Mechanisms of Disease: genetic and epigenetic alterations that drive bladder cancer.
Nat Clin Pract Urol 2:502-10 (2005)
Wu XR.
Urothelial tumorigenesis: a tale of divergent pathways.
Nat Rev Cancer 5:713-25 (2005)
Brown NS, Jones A, Fujiyama C, Harris AL, Bicknell R.
Thymidine phosphorylase induces carcinoma cell oxidative stress and promotes secretion of angiogenic factors.
Cancer Res 60:6298-302 (2000)
Bellmunt J, Hussain M, Dinney CP.
Novel approaches with targeted therapies in bladder cancer. Therapy of bladder cancer by blockade of the epidermal growth factor receptor family.
Crit Rev Oncol Hematol 46 Suppl:S85-104 (2003)
Sugano K, Kakizoe T.
Genetic alterations in bladder cancer and their clinical applications in molecular tumor staging.
Nat Clin Pract Urol 3:642-52 (2006)
Dunn KL, Espino PS, Drobic B, He S, Davie JR.
The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling.
Biochem Cell Biol 83:1-14 (2005)
Williams SG, Stein JP.
Molecular pathways in bladder cancer.
Urol Res 32:373-85 (2004)
oas04010  MAPK signaling pathway
oas04012  ErbB signaling pathway
oas04110  Cell cycle
oas04115  p53 signaling pathway
oas04370  VEGF signaling pathway
oas04520  Adherens junction
KO pathway

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