KEGG   PATHWAY: pbg05214
Entry
pbg05214                    Pathway                                
Name
Glioma - Prionailurus bengalensis (leopard cat)
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
pbg05214  Glioma
pbg05214

Organism
Prionailurus bengalensis (leopard cat) [GN:pbg]
Gene
122477450  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
122496971  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
122487677  EGFR; LOW QUALITY PROTEIN: epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
122471191  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
122472773  PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
122478872  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
122493456  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
122472604  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
122468290  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
122496268  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
122494519  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
122479809  CALML6; calmodulin-like protein 6 [KO:K02183]
122467625  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
122469437  CALM1; calmodulin-1 [KO:K02183]
122472667  calmodulin-like [KO:K02183]
122472197  calmodulin-like protein 3 [KO:K02183]
122494943  CALM3; calmodulin-3 isoform X1 [KO:K02183]
122496816  CALM2; calmodulin-2 [KO:K02183]
122473909  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D isoform X1 [KO:K08794] [EC:2.7.11.17]
122476347  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G isoform X1 [KO:K08794] [EC:2.7.11.17]
122487487  CAMK1; calcium/calmodulin-dependent protein kinase type 1 isoform X1 [KO:K08794] [EC:2.7.11.17]
122487629  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
122493437  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
122476883  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
122493468  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
122491922  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
122485801  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
122471545  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
122494748  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
122476583  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
122486600  SHC2; SHC-transforming protein 2 [KO:K17447]
122475305  SHC3; SHC-transforming protein 3 [KO:K17448]
122468671  SHC4; SHC-transforming protein 4 [KO:K17449]
122485897  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
122469065  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
122497238  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
122484176  HRAS; GTPase HRas isoform X1 [KO:K02833]
122473961  KRAS; GTPase KRas [KO:K07827]
122480981  NRAS; GTPase NRas [KO:K07828]
122477714  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
122488405  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
122487521  RAF1; LOW QUALITY PROTEIN: RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
122468485  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
122486708  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
122470517  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
122471493  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
122482064  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
122491710  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
122491934  PIK3CB; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
122487093  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
122480440  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
122489641  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
122469592  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122494042  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122476061  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122479919  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
122493436  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
122475137  cyclin-dependent kinase inhibitor 2A-like isoform X1 [KO:K06621]
122474007  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
122484900  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
122489448  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
122484101  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
122473830  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
122487880  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
122482016  RB1; retinoblastoma-associated protein [KO:K06618]
122496358  E2F1; transcription factor E2F1 [KO:K17454]
122480087  E2F2; transcription factor E2F2 [KO:K09389]
122489188  E2F3; transcription factor E2F3 [KO:K06620]
122480620  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
122486654  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
122474523  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
122494846  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
122489414  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
122484438  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
122489887  POLK; DNA polymerase kappa isoform X1 [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
PMID:15639402
  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
PMID:12154354
  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
PMID:11253051
  Authors
Holland EC.
  Title
Gliomagenesis: genetic alterations and mouse models.
  Journal
Nat Rev Genet 2:120-9 (2001)
DOI:10.1038/35052535
Reference
PMID:16700615
  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
  Authors
Tabuchi K (ed).
  Title
[Gliomas: Research and therapy] (In Japanese)
  Journal
Springer-Verlag Tokyo (2006)
Reference
PMID:12762887
  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
PMID:16095998
  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
PMID:11057895
  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
PMID:12084351
  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
pbg04010  MAPK signaling pathway
pbg04012  ErbB signaling pathway
pbg04020  Calcium signaling pathway
pbg04060  Cytokine-cytokine receptor interaction
pbg04110  Cell cycle
pbg04115  p53 signaling pathway
pbg04150  mTOR signaling pathway
KO pathway
ko05214   
LinkDB

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