KEGG   PATHWAY: mmu05214
Entry
mmu05214                    Pathway                                
Name
Glioma - Mus musculus (house mouse)
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
mmu05214  Glioma
mmu05214

Disease
H00042  Glioma
Organism
Mus musculus (house mouse) [GN:mmu]
Gene
107986  Ddb2; damage specific DNA binding protein 2 [KO:K10140]
108058  Camk2d; calcium/calmodulin-dependent protein kinase II, delta [KO:K04515] [EC:2.7.11.17]
109880  Braf; Braf transforming gene [KO:K04365] [EC:2.7.11.1]
110157  Raf1; v-raf-leukemia viral oncogene 1 [KO:K04366] [EC:2.7.11.1]
11651  Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]
11652  Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]
11836  Araf; Araf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
12018  Bak1; BCL2-antagonist/killer 1 [KO:K14021]
12028  Bax; BCL2-associated X protein [KO:K02159]
12313  Calm1; calmodulin 1 [KO:K02183]
12314  Calm2; calmodulin 2 [KO:K02183]
12315  Calm3; calmodulin 3 [KO:K02183]
12322  Camk2a; calcium/calmodulin-dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
12323  Camk2b; calcium/calmodulin-dependent protein kinase II, beta [KO:K04515] [EC:2.7.11.17]
12325  Camk2g; calcium/calmodulin-dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
12326  Camk4; calcium/calmodulin-dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
12443  Ccnd1; cyclin D1 [KO:K04503]
12567  Cdk4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
12571  Cdk6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
12575  Cdkn1a; cyclin dependent kinase inhibitor 1A [KO:K06625]
12578  Cdkn2a; cyclin dependent kinase inhibitor 2A [KO:K06621]
13197  Gadd45a; growth arrest and DNA-damage-inducible 45 alpha [KO:K04402]
13555  E2f1; E2F transcription factor 1 [KO:K17454]
13557  E2f3; E2F transcription factor 3 [KO:K06620]
13645  Egf; epidermal growth factor [KO:K04357]
13649  Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
14784  Grb2; growth factor receptor bound protein 2 [KO:K04364]
15461  Hras; Harvey rat sarcoma virus oncogene [KO:K02833]
16000  Igf1; insulin-like growth factor 1 [KO:K05459]
16001  Igf1r; insulin-like growth factor I receptor [KO:K05087] [EC:2.7.10.1]
16653  Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
17246  Mdm2; transformed mouse 3T3 cell double minute 2 [KO:K06643] [EC:2.3.2.27]
17873  Gadd45b; growth arrest and DNA-damage-inducible 45 beta [KO:K04402]
18176  Nras; neuroblastoma ras oncogene [KO:K07828]
18590  Pdgfa; platelet derived growth factor, alpha [KO:K04359]
18591  Pdgfb; platelet derived growth factor, B polypeptide [KO:K17386]
18595  Pdgfra; platelet derived growth factor receptor, alpha polypeptide [KO:K04363] [EC:2.7.10.1]
18596  Pdgfrb; platelet derived growth factor receptor, beta polypeptide [KO:K05089] [EC:2.7.10.1]
18706  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
18707  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
18708  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
18709  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
18710  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
18750  Prkca; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
18751  Prkcb; protein kinase C, beta [KO:K19662] [EC:2.7.11.13]
18752  Prkcg; protein kinase C, gamma [KO:K19663] [EC:2.7.11.13]
18803  Plcg1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
19211  Pten; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
19645  Rb1; RB transcriptional corepressor 1 [KO:K06618]
20416  Shc1; src homology 2 domain-containing transforming protein C1 [KO:K06279]
20418  Shc3; src homology 2 domain-containing transforming protein C3 [KO:K17448]
20662  Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
20663  Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
215303  Camk1g; calcium/calmodulin-dependent protein kinase I gamma [KO:K08794] [EC:2.7.11.17]
216148  Shc2; SHC (Src homology 2 domain containing) transforming protein 2 [KO:K17447]
21802  Tgfa; transforming growth factor alpha [KO:K08774]
22059  Trp53; transformation related protein 53 [KO:K04451]
227541  Camk1d; calcium/calmodulin-dependent protein kinase ID [KO:K08794] [EC:2.7.11.17]
234779  Plcg2; phospholipase C, gamma 2 [KO:K05859] [EC:3.1.4.11]
23797  Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]
23882  Gadd45g; growth arrest and DNA-damage-inducible 45 gamma [KO:K04402]
242705  E2f2; E2F transcription factor 2 [KO:K09389]
26395  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26396  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
27015  Polk; polymerase (DNA directed), kappa [KO:K03511] [EC:2.7.7.7]
271849  Shc4; SHC (Src homology 2 domain containing) family, member 4 [KO:K17449]
494124  Calm5; calmodulin 5 [KO:K02183]
52163  Camk1; calcium/calmodulin-dependent protein kinase I [KO:K08794] [EC:2.7.11.17]
56717  Mtor; mechanistic target of rapamycin kinase [KO:K07203] [EC:2.7.11.1]
70405  Calml3; calmodulin-like 3 [KO:K02183]
74769  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
75600  Calml4; calmodulin-like 4 [KO:K02183]
80796  Calm4; calmodulin 4 [KO:K02183]
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
mmu04010  MAPK signaling pathway
mmu04012  ErbB signaling pathway
mmu04020  Calcium signaling pathway
mmu04060  Cytokine-cytokine receptor interaction
mmu04110  Cell cycle
mmu04115  p53 signaling pathway
mmu04150  mTOR signaling pathway
KO pathway
ko05214   

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