KEGG   PATHWAY: umr05214
Entry
umr05214                    Pathway                                

Name
Glioma - Ursus maritimus (polar bear)
Description
Gliomas are the most common of the primary brain tumors and account for more than 40% of all central nervous system neoplasms. Gliomas include tumours that are composed predominantly of astrocytes (astrocytomas), oligodendrocytes (oligodendrogliomas), mixtures of various glial cells (for example,oligoastrocytomas) and ependymal cells (ependymomas). The most malignant form of infiltrating astrocytoma - glioblastoma multiforme (GBM) - is one of the most aggressive human cancers. GBM may develop de novo (primary glioblastoma) or by progression from low-grade or anaplastic astrocytoma (secondary glioblastoma). Primary glioblastomas develop in older patients and typically show genetic alterations (EGFR amplification, p16/INK4a deletion, and PTEN mutations) at frequencies of 24-34%. Secondary glioblastomas develop in younger patients and frequently show overexpression of PDGF and CDK4 as well as p53 mutations (65%) and loss of Rb playing major roles in such transformations. Loss of PTEN has been implicated in both pathways, although it is much more common in the pathogenesis of primary GBM.
Class
Human Diseases; Cancer: specific types
Pathway map
umr05214  Glioma
umr05214

Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103661742  EGF; epidermal growth factor [KO:K04357]
103671814  TGFA; transforming growth factor alpha [KO:K08774]
103674660  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
103670054  PDGFA; platelet derived growth factor subunit A [KO:K04359]
103676520  PDGFB; platelet derived growth factor subunit B [KO:K17386]
103672737  PDGFRA; platelet derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
103664600  PDGFRB; platelet derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
103676495  IGF1; insulin like growth factor 1 [KO:K05459]
103660044  insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
103669754  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
103662093  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
103670304  CALM1; calmodulin 1 [KO:K02183]
103682041  CALML6; calmodulin like 6 [KO:K02183]
103676238  CALML5; calmodulin like 5 [KO:K02183]
103676239  CALML3; calmodulin like 3 [KO:K02183]
103671240  CALM2; calmodulin 2 [KO:K02183]
103679049  CALML4; calmodulin like 4 [KO:K02183]
103672536  CAMK1G; calcium/calmodulin dependent protein kinase IG [KO:K08794] [EC:2.7.11.17]
103676294  CAMK1D; calcium/calmodulin dependent protein kinase ID [KO:K08794] [EC:2.7.11.17]
103661761  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
103664598  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
103668027  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
103674683  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
103675811  CAMK4; calcium/calmodulin dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
103665907  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
103668895  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
103672914  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
103668383  SHC1; SHC adaptor protein 1 [KO:K06279]
103681753  SHC2; SHC adaptor protein 2 [KO:K17447]
103663185  SHC3; SHC adaptor protein 3 [KO:K17448]
103676722  SHC4; SHC adaptor protein 4 [KO:K17449]
103665736  GRB2; growth factor receptor bound protein 2 [KO:K04364]
103671891  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
103665409  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
103669173  GTPase HRas-like [KO:K02833]
103671035  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
103665244  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
103669422  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103669103  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
103669540  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103679064  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103681834  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103669286  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103657827  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103678592  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
103666874  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103676125  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103675162  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103663617  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103670766  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103666688  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103661038  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103676878  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103666660  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
103661921  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
103656869  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
103660368  TP53; tumor protein p53 [KO:K04451]
103665536  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
103671139  CCND1; cyclin D1 [KO:K04503]
103656694  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103658796  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
103677688  RB1; RB transcriptional corepressor 1 [KO:K06618]
103674455  E2F1; E2F transcription factor 1 [KO:K17454]
103666789  E2F2; E2F transcription factor 2 [KO:K09389]
103678383  E2F3; E2F transcription factor 3 [KO:K06620]
103681651  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
103663135  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
103657107  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
103665481  putative Bcl-2 homologous antagonist/killer 2 [KO:K14021]
103672315  DDB2; damage specific DNA binding protein 2 [KO:K10140]
103663562  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Soni D, King JA, Kaye AH, Hovens CM.
  Title
Genetics of glioblastoma multiforme: mitogenic signaling and cell cycle pathways converge.
  Journal
J Clin Neurosci 12:1-5 (2005)
DOI:10.1016/j.jocn.2004.04.001
Reference
  Authors
Zhu Y, Parada LF.
  Title
The molecular and genetic basis of neurological tumours.
  Journal
Nat Rev Cancer 2:616-26 (2002)
DOI:10.1038/nrc866
Reference
  Authors
Holland EC.
  Title
Gliomagenesis: genetic alterations and mouse models.
  Journal
Nat Rev Genet 2:120-9 (2001)
DOI:10.1038/35052535
Reference
  Authors
Bansal K, Liang ML, Rutka JT.
  Title
Molecular biology of human gliomas.
  Journal
Technol Cancer Res Treat 5:185-94 (2006)
DOI:10.1177/153303460600500302
Reference
(Japanese)
  Authors
Tabuchi K (ed).
  Title
[Gliomas: Research and therapy] (In Japanese)
  Journal
Springer-Verlag Tokyo (2006)
Reference
  Authors
Kapoor GS, O'Rourke DM.
  Title
Mitogenic signaling cascades in glial tumors.
  Journal
Neurosurgery 52:1425-34; discussion 1434-5 (2003)
DOI:10.1227/01.NEU.0000065135.28143.39
Reference
  Authors
Hulleman E, Helin K.
  Title
Molecular mechanisms in gliomagenesis.
  Journal
Adv Cancer Res 94:1-27 (2005)
DOI:10.1016/S0065-230X(05)94001-3
Reference
  Authors
Schlessinger J.
  Title
Cell signaling by receptor tyrosine kinases.
  Journal
Cell 103:211-25 (2000)
DOI:10.1016/S0092-8674(00)00114-8
Reference
PMID:9643506
  Authors
Ng HK, Lam PY.
  Title
The molecular genetics of central nervous system tumors.
  Journal
Pathology 30:196-202 (1998)
DOI:10.1080/00313029800169236
Reference
  Authors
Knobbe CB, Merlo A, Reifenberger G.
  Title
Pten signaling in gliomas.
  Journal
Neuro-oncol 4:196-211 (2002)
DOI:10.1093/neuonc/4.3.196
Related
pathway
umr04010  MAPK signaling pathway
umr04012  ErbB signaling pathway
umr04020  Calcium signaling pathway
umr04060  Cytokine-cytokine receptor interaction
umr04110  Cell cycle
umr04115  p53 signaling pathway
umr04150  mTOR signaling pathway
KO pathway
ko05214   
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