KEGG   PATHWAY: mcal05219
mcal05219                   Pathway                                

Bladder cancer - Mus caroli (Ryukyu mouse)
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
mcal05219  Bladder cancer

Mus caroli (Ryukyu mouse) [GN:mcal]
110293909  Fgfr3; fibroblast growth factor receptor 3 [KO:K05094] [EC:]
110297313  Hras; GTPase HRas isoform X1 [KO:K02833]
110296194  Kras; GTPase KRas isoform X1 [KO:K07827]
110290873  Nras; GTPase NRas [KO:K07828]
110287540  Araf; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:]
110295945  Braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:]
110296919  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:]
110301502  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:]
110303196  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:]
110297836  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
110311382  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
110306698  Rps6ka5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:]
110310583  Myc; myc proto-oncogene protein [KO:K04377]
110301468  Rassf1; ras association domain-containing protein 1 isoform X1 [KO:K09850]
110301682  Dapk2; death-associated protein kinase 2 [KO:K08803] [EC:]
110307645  Dapk1; death-associated protein kinase 1 isoform X1 [KO:K08803] [EC:]
110303111  Dapk3; death-associated protein kinase 3 isoform X1 [KO:K08803] [EC:]
110293174  cyclin-dependent kinase inhibitor 2A [KO:K06621]
110303712  Mdm2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:]
110305297  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
110283679  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
110298189  Ccnd1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
110303132  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:]
110309179  Rb1; retinoblastoma-associated protein [KO:K06618]
110289983  E2f1; transcription factor E2F1 isoform X1 [KO:K17454]
110293508  E2f2; transcription factor E2F2 [KO:K09389]
110308034  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
110310932  Thbs1; thrombospondin-1 [KO:K16857]
110285141  Hbegf; proheparin-binding EGF-like growth factor [KO:K08523]
110299708  Mmp2; 72 kDa type IV collagenase [KO:K01398] [EC:]
110290048  Mmp9; matrix metalloproteinase-9 isoform X1 [KO:K01403] [EC:]
110310977  Upk3a; uroplakin-3a isoform X1 [KO:K19520]
110310031  Src; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:]
110291005  Egf; pro-epidermal growth factor isoform X1 [KO:K04357]
110304771  Erbb2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:]
110304228  Egfr; epidermal growth factor receptor [KO:K04361] [EC:]
110310004  Tymp; thymidine phosphorylase [KO:K00758] [EC:]
110284402  Vegfa; vascular endothelial growth factor A isoform X1 [KO:K05448]
110302197  interstitial collagenase A [KO:K01388] [EC:]
110302562  interstitial collagenase B [KO:K01388] [EC:]
110300286  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)
mcal04010  MAPK signaling pathway
mcal04012  ErbB signaling pathway
mcal04110  Cell cycle
mcal04115  p53 signaling pathway
mcal04370  VEGF signaling pathway
mcal04520  Adherens junction
KO pathway

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