KEGG   PATHWAY: mmu05219
Entry
mmu05219                    Pathway                                
Name
Bladder cancer - Mus musculus (house mouse)
Description
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).
Class
Human Diseases; Cancer: specific types
Pathway map
mmu05219  Bladder cancer
mmu05219

Organism
Mus musculus (house mouse) [GN:mmu]
Gene
14184  Fgfr3; fibroblast growth factor receptor 3 [KO:K05094] [EC:2.7.10.1]
15461  Hras; Harvey rat sarcoma virus oncogene [KO:K02833]
16653  Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
18176  Nras; neuroblastoma ras oncogene [KO:K07828]
11836  Araf; Araf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
109880  Braf; Braf transforming gene [KO:K04365] [EC:2.7.11.1]
110157  Raf1; v-raf-leukemia viral oncogene 1 [KO:K04366] [EC:2.7.11.1]
26395  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26396  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
73086  Rps6ka5; ribosomal protein S6 kinase, polypeptide 5 [KO:K04445] [EC:2.7.11.1]
17869  Myc; myelocytomatosis oncogene [KO:K04377]
56289  Rassf1; Ras association (RalGDS/AF-6) domain family member 1 [KO:K09850]
13143  Dapk2; death-associated protein kinase 2 [KO:K08803] [EC:2.7.11.1]
13144  Dapk3; death-associated protein kinase 3 [KO:K08803] [EC:2.7.11.1]
69635  Dapk1; death associated protein kinase 1 [KO:K08803] [EC:2.7.11.1]
12578  Cdkn2a; cyclin dependent kinase inhibitor 2A [KO:K06621]
17246  Mdm2; transformed mouse 3T3 cell double minute 2 [KO:K06643] [EC:2.3.2.27]
22059  Trp53; transformation related protein 53 [KO:K04451]
12575  Cdkn1a; cyclin-dependent kinase inhibitor 1A (P21) [KO:K06625]
12443  Ccnd1; cyclin D1 [KO:K04503]
12567  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
19645  Rb1; RB transcriptional corepressor 1 [KO:K06618]
13555  E2f1; E2F transcription factor 1 [KO:K17454]
242705  E2f2; E2F transcription factor 2 [KO:K09389]
13557  E2f3; E2F transcription factor 3 [KO:K06620]
21825  Thbs1; thrombospondin 1 [KO:K16857]
15200  Hbegf; heparin-binding EGF-like growth factor [KO:K08523]
17390  Mmp2; matrix metallopeptidase 2 [KO:K01398] [EC:3.4.24.24]
17395  Mmp9; matrix metallopeptidase 9 [KO:K01403] [EC:3.4.24.35]
22270  Upk3a; uroplakin 3A [KO:K19520]
20779  Src; Rous sarcoma oncogene [KO:K05704] [EC:2.7.10.2]
13645  Egf; epidermal growth factor [KO:K04357]
13866  Erbb2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
13649  Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
72962  Tymp; thymidine phosphorylase [KO:K00758] [EC:2.4.2.4]
22339  Vegfa; vascular endothelial growth factor A [KO:K05448]
83995  Mmp1a; matrix metallopeptidase 1a (interstitial collagenase) [KO:K01388] [EC:3.4.24.7]
83996  Mmp1b; matrix metallopeptidase 1b (interstitial collagenase) [KO:K01388] [EC:3.4.24.7]
12550  Cdh1; cadherin 1 [KO:K05689]
Reference
  Authors
Mitra AP, Datar RH, Cote RJ.
  Title
Molecular pathways in invasive bladder cancer: new insights into mechanisms, progression, and target identification.
  Journal
J Clin Oncol 24:5552-64 (2006)
DOI:10.1200/JCO.2006.08.2073
Reference
  Authors
Wolff EM, Liang G, Jones PA.
  Title
Mechanisms of Disease: genetic and epigenetic alterations that drive bladder cancer.
  Journal
Nat Clin Pract Urol 2:502-10 (2005)
DOI:10.1038/ncpuro0318
Reference
  Authors
Wu XR.
  Title
Urothelial tumorigenesis: a tale of divergent pathways.
  Journal
Nat Rev Cancer 5:713-25 (2005)
DOI:10.1038/nrc1697
Reference
  Authors
Brown NS, Jones A, Fujiyama C, Harris AL, Bicknell R.
  Title
Thymidine phosphorylase induces carcinoma cell oxidative stress and promotes secretion of angiogenic factors.
  Journal
Cancer Res 60:6298-302 (2000)
Reference
  Authors
Bellmunt J, Hussain M, Dinney CP.
  Title
Novel approaches with targeted therapies in bladder cancer. Therapy of bladder cancer by blockade of the epidermal growth factor receptor family.
  Journal
Crit Rev Oncol Hematol 46 Suppl:S85-104 (2003)
DOI:10.1016/S1040-8428(03)00067-2
Reference
  Authors
Sugano K, Kakizoe T.
  Title
Genetic alterations in bladder cancer and their clinical applications in molecular tumor staging.
  Journal
Nat Clin Pract Urol 3:642-52 (2006)
DOI:10.1038/ncpuro0649
Reference
  Authors
Dunn KL, Espino PS, Drobic B, He S, Davie JR.
  Title
The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling.
  Journal
Biochem Cell Biol 83:1-14 (2005)
DOI:10.1139/o04-121
Reference
  Authors
Williams SG, Stein JP.
  Title
Molecular pathways in bladder cancer.
  Journal
Urol Res 32:373-85 (2004)
DOI:10.1007/s00240-003-0345-y
Related
pathway
mmu04010  MAPK signaling pathway
mmu04012  ErbB signaling pathway
mmu04110  Cell cycle
mmu04115  p53 signaling pathway
mmu04370  VEGF signaling pathway
mmu04520  Adherens junction
KO pathway
ko05219   
LinkDB

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