KEGG   PATHWAY: ngi05214
Entry
ngi05214                    Pathway                                

Name
Glioma - Nannospalax galili (Upper Galilee mountains blind mole rat)
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
ngi05214  Glioma
ngi05214

Organism
Nannospalax galili (Upper Galilee mountains blind mole rat) [GN:ngi]
Gene
103742642  Egf; epidermal growth factor [KO:K04357]
103725901  Tgfa; transforming growth factor alpha [KO:K08774]
103748852  epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
103748699  Pdgfa; platelet derived growth factor subunit A [KO:K04359]
103748570  Pdgfb; platelet derived growth factor subunit B [KO:K17386]
103734393  Pdgfra; platelet derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
103747076  Pdgfrb; platelet derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
103733723  Igf1; insulin like growth factor 1 [KO:K05459]
103749467  Igf1r; insulin like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
103747244  Plcg1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
103748739  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
103725694  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2-like [KO:K05859] [EC:3.1.4.11]
103737134  Calml3; calmodulin like 3 [KO:K02183]
103737133  Calml5; calmodulin like 5 [KO:K02183]
103749800  Calml6; calmodulin like 6 [KO:K02183]
103724616  Calm1; calmodulin 1 [KO:K02183]
103724738  Calm3; calmodulin 3 [KO:K02183]
103725745  Calm2; calmodulin 2 [KO:K02183]
103729208  calmodulin-alpha-like [KO:K02183]
103736816  Calml4; calmodulin like 4 [KO:K02183]
103746367  Camk1d; calcium/calmodulin dependent protein kinase ID [KO:K08794] [EC:2.7.11.17]
103751418  Camk1; calcium/calmodulin dependent protein kinase I [KO:K08794] [EC:2.7.11.17]
103727073  Camk1g; calcium/calmodulin dependent protein kinase IG [KO:K08794] [EC:2.7.11.17]
103736933  Camk2g; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
103734983  Camk2b; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
103743264  Camk2d; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
103747079  Camk2a; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
103752296  Camk4; calcium/calmodulin dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
103742202  Prkca; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
103746928  Prkcb; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
103729666  Prkcg; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
103751254  Shc1; SHC adaptor protein 1 [KO:K06279]
103737407  Shc2; SHC adaptor protein 2 [KO:K17447]
103726215  Shc3; SHC adaptor protein 3 [KO:K17448]
103733036  Shc4; SHC adaptor protein 4 [KO:K17449]
103732729  Grb2; growth factor receptor bound protein 2 [KO:K04364]
103743944  Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
103731514  Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
103751075  Hras; HRas proto-oncogene, GTPase [KO:K02833]
103736717  Kras; KRAS proto-oncogene, GTPase [KO:K07827]
103734938  Nras; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103741627  Araf; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
103726107  Braf; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
103751450  Raf1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103736801  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103737276  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103741442  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103726390  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103738596  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103733121  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103742946  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
103738715  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103726879  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103730305  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103746884  Akt3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103750757  Akt2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103752536  Akt1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103732897  Mtor; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
103738044  Pten; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
103730663  cyclin-dependent kinase 4 inhibitor B-like [KO:K06621]
103745079  Mdm2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
103752115  Tp53; tumor protein p53 [KO:K04451]
103739652  Cdkn1a; cyclin dependent kinase inhibitor 1A [KO:K06625]
103751498  Ccnd1; cyclin D1 [KO:K04503]
103742900  Cdk4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103725210  Cdk6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
103726779  Rb1; RB transcriptional corepressor 1 [KO:K06618]
103751571  E2f1; E2F transcription factor 1 [KO:K17454]
103746411  E2f2; E2F transcription factor 2 [KO:K09389]
103745641  E2f3; E2F transcription factor 3 [KO:K06620]
103737285  Gadd45b; growth arrest and DNA damage inducible beta [KO:K04402]
103743354  Gadd45a; growth arrest and DNA damage inducible alpha [KO:K04402]
103751225  Gadd45g; growth arrest and DNA damage inducible gamma [KO:K04402]
103743639  Bax; BCL2 associated X, apoptosis regulator [KO:K02159]
103739733  Bak1; BCL2 antagonist/killer 1 [KO:K14021]
103742505  Ddb2; damage specific DNA binding protein 2 [KO:K10140]
103736569  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
ngi04010  MAPK signaling pathway
ngi04012  ErbB signaling pathway
ngi04020  Calcium signaling pathway
ngi04060  Cytokine-cytokine receptor interaction
ngi04110  Cell cycle
ngi04115  p53 signaling pathway
ngi04150  mTOR signaling pathway
KO pathway
ko05214   
LinkDB

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