KEGG   PATHWAY: mmu05222Help
Entry
mmu05222                    Pathway                                

Name
Small cell lung cancer - Mus musculus (mouse)
Description
Lung cancer is a leading cause of cancer death among men and women in industrialized countries. Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 25% of all lung cancer cases.  Molecular mechanisms altered in SCLC include induced expression of oncogene, MYC, and loss of tumorsuppressor genes, such as p53, PTEN, RB, and FHIT. The overexpression of MYC proteins in SCLC is largely a result of gene amplification. Such overexpression leads to more rapid proliferation and loss of terminal differentiation. Mutation or deletion of p53 or PTEN can lead to more rapid proliferation and reduced apoptosis. The retinoblastoma gene RB1 encodes a nuclear phosphoprotein that helps to regulate cell-cycle progression. The fragile histidine triad gene FHIT encodes the enzyme diadenosine triphosphate hydrolase, which is thought to have an indirect role in proapoptosis and cell-cycle control.
Class
Human Diseases; Cancers
BRITE hierarchy
Pathway map
Small cell lung cancer
mmu05222

All organismsOrtholog table
Organism
Mus musculus (mouse) [GN:mmu]
Gene
14198  
Fhit; fragile histidine triad gene [KO:K01522] [EC:3.6.1.29]
218772  
Rarb; retinoic acid receptor, beta [KO:K08528]
20181  
Rxra; retinoid X receptor alpha [KO:K08524]
20182  
Rxrb; retinoid X receptor beta [KO:K08525]
20183  
Rxrg; retinoid X receptor gamma [KO:K08526]
22059  
Trp53; transformation related protein 53 [KO:K04451]
12575  
Cdkn1a; cyclin-dependent kinase inhibitor 1A (P21) [KO:K06625]
13197  
Gadd45a; growth arrest and DNA-damage-inducible 45 alpha [KO:K04402]
17873  
Gadd45b; growth arrest and DNA-damage-inducible 45 beta [KO:K04402]
23882  
Gadd45g; growth arrest and DNA-damage-inducible 45 gamma [KO:K04402]
12028  
Bax; BCL2-associated X protein [KO:K02159]
12018  
Bak1; BCL2-antagonist/killer 1 [KO:K14021]
107986  
Ddb2; damage specific DNA binding protein 2 [KO:K10140]
27015  
Polk; polymerase (DNA directed), kappa [KO:K03511] [EC:2.7.7.7]
12043  
Bcl2; B cell leukemia/lymphoma 2 [KO:K02161]
13063  
Cycs; cytochrome c, somatic [KO:K08738]
13067  
Cyct; cytochrome c, testis [KO:K08738]
11783  
Apaf1; apoptotic peptidase activating factor 1 [KO:K02084]
12371  
Casp9; caspase 9 [KO:K04399] [EC:3.4.22.62]
12367  
Casp3; caspase 3 [KO:K02187] [EC:3.4.22.56]
17869  
Myc; myelocytomatosis oncogene [KO:K04377]
17187  
Max; Max protein [KO:K04453]
22642  
Zbtb17; zinc finger and BTB domain containing 17 [KO:K10500]
12579  
Cdkn2b; cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) [KO:K04685]
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]
12443  
Ccnd1; cyclin D1 [KO:K04503]
54124  
Cks1b; CDC28 protein kinase 1b [KO:K02219]
66197  
Cks2; CDC28 protein kinase regulatory subunit 2 [KO:K02219]
27401  
Skp2; S-phase kinase-associated protein 2 (p45) [KO:K03875]
12576  
Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
12566  
Cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
12447  
Ccne1; cyclin E1 [KO:K06626]
12448  
Ccne2; cyclin E2 [KO:K06626]
19645  
Rb1; RB transcriptional corepressor 1 [KO:K06618]
13555  
E2f1; E2F transcription factor 1 [KO:K17454]
242705  
E2f2; E2F transcription factor 2 [KO:K09389]
13557  
E2f3; E2F transcription factor 3 [KO:K06620]
12826  
Col4a1; collagen, type IV, alpha 1 [KO:K06237]
12827  
Col4a2; collagen, type IV, alpha 2 [KO:K06237]
12829  
Col4a4; collagen, type IV, alpha 4 [KO:K06237]
94216  
Col4a6; collagen, type IV, alpha 6 [KO:K06237]
12830  
Col4a5; collagen, type IV, alpha 5 [KO:K06237]
12828  
Col4a3; collagen, type IV, alpha 3 [KO:K06237]
16772  
Lama1; laminin, alpha 1 [KO:K05637]
16773  
Lama2; laminin, alpha 2 [KO:K05637]
16774  
Lama3; laminin, alpha 3 [KO:K06240]
16776  
Lama5; laminin, alpha 5 [KO:K06240]
16775  
Lama4; laminin, alpha 4 [KO:K06241]
16777  
Lamb1; laminin B1 [KO:K05636]
16779  
Lamb2; laminin, beta 2 [KO:K06243]
16780  
Lamb3; laminin, beta 3 [KO:K06244]
226519  
Lamc1; laminin, gamma 1 [KO:K05635]
16782  
Lamc2; laminin, gamma 2 [KO:K06246]
23928  
Lamc3; laminin gamma 3 [KO:K06247]
14268  
Fn1; fibronectin 1 [KO:K05717]
16398  
Itga2; integrin alpha 2 [KO:K06481]
16399  
Itga2b; integrin alpha 2b [KO:K06476]
16400  
Itga3; integrin alpha 3 [KO:K06482]
16403  
Itga6; integrin alpha 6 [KO:K06485]
16410  
Itgav; integrin alpha V [KO:K06487]
16412  
Itgb1; integrin beta 1 (fibronectin receptor beta) [KO:K05719]
14083  
Ptk2; PTK2 protein tyrosine kinase 2 [KO:K05725] [EC:2.7.10.2]
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]
74769  
Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
18709  
Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
18708  
Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
18710  
Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
19211  
Pten; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.67 3.1.3.48 3.1.3.16]
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]
23797  
Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]
12675  
Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
16150  
Ikbkb; inhibitor of kappaB kinase beta [KO:K07209] [EC:2.7.11.10]
16151  
Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210]
18035  
Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha [KO:K04734]
18033  
Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580]
19697  
Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
11797  
Birc2; baculoviral IAP repeat-containing 2 [KO:K16060]
11796  
Birc3; baculoviral IAP repeat-containing 3 [KO:K16060]
11798  
Xiap; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
329581  
Birc7; baculoviral IAP repeat-containing 7 (livin) [KO:K16061]
12048  
Bcl2l1; BCL2-like 1 [KO:K04570]
22029  
Traf1; TNF receptor-associated factor 1 [KO:K03172]
22030  
Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
22031  
Traf3; TNF receptor-associated factor 3 [KO:K03174]
22032  
Traf4; TNF receptor associated factor 4 [KO:K09848]
22033  
Traf5; TNF receptor-associated factor 5 [KO:K09849]
22034  
Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
19225  
Ptgs2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
18126  
Nos2; nitric oxide synthase 2, inducible [KO:K13241] [EC:1.14.13.39]
Compound
C00777  
Retinoate
C05981  
Phosphatidylinositol-3,4,5-trisphosphate
C15493  
9-cis-Retinoic acid
Reference
  Authors
Osada H, Takahashi T.
  Title
Genetic alterations of multiple tumor suppressors and oncogenes in the carcinogenesis and progression of lung cancer.
  Journal
Oncogene 21:7421-34 (2002)
DOI:10.1038/sj.onc.1205802
Reference
  Authors
Yokota J, Nishioka M, Tani M, Kohno T.
  Title
Genetic alterations responsible for metastatic phenotypes of lung cancer cells.
  Journal
Clin Exp Metastasis 20:189-93 (2003)
Reference
  Authors
Sanchez-Cespedes M.
  Title
Dissecting the genetic alterations involved in lung carcinogenesis.
  Journal
Lung Cancer 40:111-21 (2003)
DOI:10.1016/S0169-5002(03)00033-3
Reference
  Authors
Mitsuuchi Y, Testa JR.
  Title
Cytogenetics and molecular genetics of lung cancer.
  Journal
Am J Med Genet 115:183-8 (2002)
DOI:10.1002/ajmg.10692
Reference
  Authors
Kaye FJ.
  Title
Molecular biology of lung cancer.
  Journal
Lung Cancer 34 Suppl 2:S35-41 (2001)
DOI:10.1016/S0169-5002(01)00342-7
Reference
  Authors
Panani AD, Roussos C.
  Title
Cytogenetic and molecular aspects of lung cancer.
  Journal
Cancer Lett 239:1-9 (2006)
DOI:10.1016/j.canlet.2005.06.030
Reference
  Authors
Altucci L, Gronemeyer H.
  Title
The promise of retinoids to fight against cancer.
  Journal
Nat Rev Cancer 1:181-93 (2001)
DOI:10.1038/35106036
Reference
  Authors
Virmani AK, Rathi A, Zochbauer-Muller S, Sacchi N, Fukuyama Y, Bryant D, Maitra A, Heda S, Fong KM, Thunnissen F, Minna JD, Gazdar AF.
  Title
Promoter methylation and silencing of the retinoic acid receptor-beta gene in lung carcinomas.
  Journal
J Natl Cancer Inst 92:1303-7 (2000)
DOI:10.1093/jnci/92.16.1303
Reference
  Authors
Sartorius UA, Krammer PH.
  Title
Upregulation of Bcl-2 is involved in the mediation of chemotherapy resistance in human small cell lung cancer cell lines.
  Journal
Int J Cancer 97:584-92 (2002)
DOI:10.1002/ijc.10096
Reference
  Authors
Adhikary S, Eilers M.
  Title
Transcriptional regulation and transformation by Myc proteins.
  Journal
Nat Rev Mol Cell Biol 6:635-45 (2005)
DOI:10.1038/nrm1703
Reference
  Authors
Spruck C, Strohmaier H, Watson M, Smith AP, Ryan A, Krek TW, Reed SI.
  Title
A CDK-independent function of mammalian Cks1: targeting of SCF(Skp2) to the CDK inhibitor p27Kip1.
  Journal
Mol Cell 7:639-50 (2001)
DOI:10.1016/S1097-2765(01)00210-6
Reference
  Authors
Buttery RC, Rintoul RC, Sethi T.
  Title
Small cell lung cancer: the importance of the extracellular matrix.
  Journal
Int J Biochem Cell Biol 36:1154-60 (2004)
DOI:10.1016/S1357-2725(03)00261-9
Reference
  Authors
Yamada KM, Araki M.
  Title
Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis.
  Journal
J Cell Sci 114:2375-82 (2001)
Reference
  Authors
Rintoul RC, Sethi T.
  Title
The role of extracellular matrix in small-cell lung cancer.
  Journal
Lancet Oncol 2:437-42 (2001)
DOI:10.1016/S1470-2045(00)00421-6
Reference
  Authors
Ekedahl J, Joseph B, Grigoriev MY, Muller M, Magnusson C, Lewensohn R, Zhivotovsky B.
  Title
Expression of inhibitor of apoptosis proteins in small- and non-small-cell lung carcinoma cells.
  Journal
Exp Cell Res 279:277-90 (2002)
DOI:10.1006/excr.2002.5608
Reference
  Authors
Shivapurkar N, Reddy J, Chaudhary PM, Gazdar AF.
  Title
Apoptosis and lung cancer: a review.
  Journal
J Cell Biochem 88:885-98 (2003)
DOI:10.1002/jcb.10440
Reference
  Authors
Weyhenmeyer B, Murphy AC, Prehn JH, Murphy BM
  Title
Targeting the anti-apoptotic Bcl-2 family members for the treatment of cancer.
  Journal
Exp Oncol 34:192-9 (2012)
KO pathway
 

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