KEGG   PATHWAY: mcc05214
Entry
mcc05214                    Pathway                                

Name
Glioma - Macaca mulatta (rhesus monkey)
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
mcc05214  Glioma
mcc05214

Organism
Macaca mulatta (rhesus monkey) [GN:mcc]
Gene
698619  EGF; pro-epidermal growth factor isoform X2 [KO:K04357]
613031  TGFA; protransforming growth factor alpha isoform X2 [KO:K08774]
613027  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
707725  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
703173  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
697002  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
711353  PDGFRB; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
698444  IGF1; insulin-like growth factor I precursor [KO:K05459]
708227  IGF1R; insulin-like growth factor 1 receptor precursor [KO:K05087] [EC:2.7.10.1]
697069  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
714173  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
717686  calmodulin [KO:K02183]
698552  CALM1; calmodulin-1 isoform X1 [KO:K02183]
715270  CALM2; calmodulin-2 [KO:K02183]
703514  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
712159  CALML5; calmodulin-like protein 5 [KO:K02183]
722513  CALML3; calmodulin-like protein 3 [KO:K02183]
716584  CALM3; calmodulin-3 isoform X1 [KO:K02183]
693753  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
706351  calmodulin-like [KO:K02183]
697661  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D isoform X3 [KO:K08794] [EC:2.7.11.17]
700212  CAMK1; calcium/calmodulin-dependent protein kinase type 1 [KO:K08794] [EC:2.7.11.17]
717624  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G isoform X2 [KO:K08794] [EC:2.7.11.17]
705980  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
702504  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515] [EC:2.7.11.17]
706977  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X11 [KO:K04515] [EC:2.7.11.17]
710540  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
712322  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
718412  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
701195  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
720263  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
718982  SHC1; SHC-transforming protein 1 [KO:K06279]
721021  SHC2; SHC-transforming protein 2 [KO:K17447]
574275  SHC3; SHC-transforming protein 3 [KO:K17448]
714611  SHC4; SHC-transforming protein 4 [KO:K17449]
702041  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
713777  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
705601  SOS2; son of sevenless homolog 2 [KO:K03099]
698830  HRAS; GTPase HRas [KO:K02833]
707977  KRAS; GTPase KRas [KO:K07827]
709089  NRAS; GTPase NRas [KO:K07828]
707169  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
693554  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
694725  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
710415  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
721821  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
708938  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
698569  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
716098  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
709959  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
710552  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
707310  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
719367  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
698996  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
714717  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
697747  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
700591  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
106992736  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
705121  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
709988  cyclin-dependent kinase inhibitor 2A [KO:K06621]
718284  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
716170  TP53; cellular tumor antigen p53 [KO:K04451]
719199  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
574320  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
715650  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
701822  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
704871  RB1; retinoblastoma-associated protein [KO:K06618]
714126  E2F1; transcription factor E2F1 [KO:K17454]
710200  E2F2; transcription factor E2F2 [KO:K09389]
713904  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
697835  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
701054  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
711257  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
718948  BAX; apoptosis regulator BAX [KO:K02159]
706534  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
114675515  bcl-2 homologous antagonist/killer-like [KO:K14021]
713813  DDB2; DNA damage-binding protein 2 [KO:K10140]
114672263  LOW QUALITY PROTEIN: DNA damage-binding protein 2-like [KO:K10140]
705713  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
  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
mcc04010  MAPK signaling pathway
mcc04012  ErbB signaling pathway
mcc04020  Calcium signaling pathway
mcc04060  Cytokine-cytokine receptor interaction
mcc04110  Cell cycle
mcc04115  p53 signaling pathway
mcc04150  mTOR signaling pathway
KO pathway
ko05214   
LinkDB

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