KEGG   PATHWAY: ocu05219
Entry
ocu05219                    Pathway                                

Name
Bladder cancer - Oryctolagus cuniculus (rabbit)
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
ocu05219  Bladder cancer
ocu05219

Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
100347487  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
100344241  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
100340437  ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
100351964  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
100347407  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
100009316  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100347345  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100348561  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100348520  RPS6KA5; ribosomal protein S6 kinase A5 [KO:K04445] [EC:2.7.11.1]
100327265  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
100340832  RASSF1; Ras association domain family member 1 [KO:K09850]
100343775  DAPK1; death associated protein kinase 1 [KO:K08803] [EC:2.7.11.1]
100352862  DAPK2; death associated protein kinase 2 [KO:K08803] [EC:2.7.11.1]
100340625  CDKN2A; cyclin-dependent kinase inhibitor 2A [KO:K06621]
100340389  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
100009292  TP53; tumor protein p53 [KO:K04451]
100348489  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
100009039  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
100357431  RB1; RB transcriptional corepressor 1 [KO:K06618]
100356957  E2F1; E2F transcription factor 1 [KO:K17454]
100346379  E2F2; E2F transcription factor 2 [KO:K09389]
100353173  E2F3; E2F transcription factor 3 [KO:K06620]
100350430  THBS1; thrombospondin 1 [KO:K16857]
100008809  HBEGF; heparin binding EGF like growth factor [KO:K08523]
100009000  MMP2; matrix metallopeptidase 2 [KO:K01398] [EC:3.4.24.24]
100008993  MMP9; matrix metallopeptidase 9 [KO:K01403] [EC:3.4.24.35]
100358839  UPK3A; uroplakin 3A [KO:K19520]
100341599  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
100008808  EGF; epidermal growth factor [KO:K04357]
100009554  ERBB2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
100008806  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
100348459  TYMP; thymidine phosphorylase [KO:K00758] [EC:2.4.2.4]
100008899  VEGFA; vascular endothelial growth factor A [KO:K05448]
100009110  MMP1; matrix metallopeptidase 1 [KO:K01388] [EC:3.4.24.7]
100009129  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
100356548  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
ocu04010  MAPK signaling pathway
ocu04012  ErbB signaling pathway
ocu04110  Cell cycle
ocu04115  p53 signaling pathway
ocu04370  VEGF signaling pathway
ocu04520  Adherens junction
KO pathway
ko05219   
LinkDB

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