KEGG   PATHWAY: mmu05212Help
Entry
mmu05212                    Pathway                                

Name
Pancreatic cancer - Mus musculus (mouse)
Description
Infiltrating ductal adenocarcinoma is the most common malignancy of the pancreas. When most investigators use the term 'pancreatic cancer' they are referring to pancreatic ductal adenocarcinoma (PDA). Normal duct epithelium progresses to infiltrating cancer through a series of histologically defined precursors (PanINs). The overexpression of HER-2/neu and activating point mutations in the K-ras gene occur early, inactivation of the p16 gene at an intermediate stage, and the inactivation of p53, SMAD4, and BRCA2 occur relatively late. Activated K-ras engages multiple effector pathways.  Although EGF receptors are conventionally regarded as upstream activators of RAS proteins, they can also act as RAS signal transducers via RAS-induced autocrine activation of the EGFR family ligands. Moreover, PDA shows extensive genomic instability and aneuploidy. Telomere attrition and mutations in p53 and BRCA2 are likely to contribute to these phenotypes. Inactivation of the SMAD4 tumour suppressor gene leads to loss of the inhibitory influence of the transforming growth factor-beta signalling pathway.
Class
Human Diseases; Cancers
BRITE hierarchy
Pathway map
Pancreatic cancer
mmu05212

All organismsOrtholog table
Organism
Mus musculus (mouse) [GN:mmu]
Gene
16653  
Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
30955  
Pik3cg; phosphoinositide-3-kinase, catalytic, gamma polypeptide [KO:K00922] [EC:2.7.1.153]
18706  
Pik3ca; phosphatidylinositol 3-kinase, catalytic, alpha polypeptide [KO:K00922] [EC:2.7.1.153]
18707  
Pik3cd; phosphatidylinositol 3-kinase catalytic delta polypeptide [KO:K00922] [EC:2.7.1.153]
74769  
Pik3cb; phosphatidylinositol 3-kinase, catalytic, beta polypeptide [KO:K00922] [EC:2.7.1.153]
18709  
Pik3r2; phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 2 (p85 beta) [KO:K02649]
18708  
Pik3r1; phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha) [KO:K02649]
320207  
Pik3r5; phosphoinositide-3-kinase, regulatory subunit 5, p101 [KO:K02649]
18710  
Pik3r3; phosphatidylinositol 3 kinase, regulatory subunit, polypeptide 3 (p55) [KO:K02649]
73341  
Arhgef6; Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6 [KO:K05729]
19353  
Rac1; RAS-related C3 botulinum substrate 1 [KO:K04392]
19354  
Rac2; RAS-related C3 botulinum substrate 2 [KO:K07860]
170758  
Rac3; RAS-related C3 botulinum substrate 3 [KO:K07861]
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]
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]
12015  
Bad; BCL2-associated agonist of cell death [KO:K02158]
12048  
Bcl2l1; BCL2-like 1 [KO:K04570]
12371  
Casp9; caspase 9 [KO:K04399] [EC:3.4.22.62]
11836  
Araf; Araf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
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]
26395  
Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [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]
26419  
Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
26420  
Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
26414  
Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
19730  
Ralgds; ral guanine nucleotide dissociation stimulator [KO:K08732]
56044  
Rala; v-ral simian leukemia viral oncogene A (ras related) [KO:K07834]
64143  
Ralb; v-ral simian leukemia viral oncogene B [KO:K07835]
19765  
Ralbp1; ralA binding protein 1 [KO:K08773]
12540  
Cdc42; cell division cycle 42 [KO:K04393]
21802  
Tgfa; transforming growth factor alpha [KO:K08774]
13645  
Egf; epidermal growth factor [KO:K04357]
13649  
Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
13866  
Erbb2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
16451  
Jak1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
20848  
Stat3; signal transducer and activator of transcription 3 [KO:K04692]
20846  
Stat1; signal transducer and activator of transcription 1 [KO:K11220]
22339  
Vegfa; vascular endothelial growth factor A [KO:K05448]
12578  
Cdkn2a; cyclin-dependent kinase inhibitor 2A [KO:K06621]
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]
19645  
Rb1; retinoblastoma 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]
22059  
Trp53; transformation related protein 53 [KO:K04451]
21803  
Tgfb1; transforming growth factor, beta 1 [KO:K13375]
21808  
Tgfb2; transforming growth factor, beta 2 [KO:K13376]
21809  
Tgfb3; transforming growth factor, beta 3 [KO:K13377]
21812  
Tgfbr1; transforming growth factor, beta receptor I [KO:K04674] [EC:2.7.11.30]
21813  
Tgfbr2; transforming growth factor, beta receptor II [KO:K04388] [EC:2.7.11.30]
17126  
Smad2; SMAD family member 2 [KO:K04500]
17127  
Smad3; SMAD family member 3 [KO:K04500]
17128  
Smad4; SMAD family member 4 [KO:K04501]
12190  
Brca2; breast cancer 2, early onset [KO:K08775]
19361  
Rad51; RAD51 recombinase [KO:K04482]
18805  
Pld1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
Compound
C00416  
Phosphatidate
C05981  
Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Von Hoff D, Evans D, Hruban R (ed).
  Title
Pancreatic cancer
  Journal
Jones and Bartlett publishers (2005)
Reference
(Japanese)
  Authors
Niitsu Y, Yokota J (ed).
  Title
[Oncogenes and Tumor Suppressor Genes for Medical Oncologist] (In Japanese)
  Journal
Nankodo (1999)
Reference
  Authors
Bardeesy N, DePinho RA.
  Title
Pancreatic cancer biology and genetics.
  Journal
Nat Rev Cancer 2:897-909 (2002)
Reference
  Authors
Bardeesy N, Sharpless NE, DePinho RA, Merlino G.
  Title
The genetics of pancreatic adenocarcinoma: a roadmap for a mouse model.
  Journal
Semin Cancer Biol 11:201-18 (2001)
Reference
  Authors
Cowgill SM, Muscarella P.
  Title
The genetics of pancreatic cancer.
  Journal
Am J Surg 186:279-86 (2003)
Reference
  Authors
Hezel AF, Kimmelman AC, Stanger BZ, Bardeesy N, Depinho RA.
  Title
Genetics and biology of pancreatic ductal adenocarcinoma.
  Journal
Genes Dev 20:1218-49 (2006)
Reference
  Authors
Shields JM, Pruitt K, McFall A, Shaub A, Der CJ.
  Title
Understanding Ras: 'it ain't over 'til it's over'.
  Journal
Trends Cell Biol 10:147-54 (2000)
Reference
  Authors
Holbro T, Civenni G, Hynes NE.
  Title
The ErbB receptors and their role in cancer progression.
  Journal
Exp Cell Res 284:99-110 (2003)
Reference
  Authors
Marmor MD, Skaria KB, Yarden Y.
  Title
Signal transduction and oncogenesis by ErbB/HER receptors.
  Journal
Int J Radiat Oncol Biol Phys 58:903-13 (2004)
Reference
  Authors
DeArmond D, Brattain MG, Jessup JM, Kreisberg J, Malik S, Zhao S, Freeman JW.
  Title
Autocrine-mediated ErbB-2 kinase activation of STAT3 is required for growth factor independence of pancreatic cancer cell lines.
  Journal
Oncogene 22:7781-95 (2003)
Reference
  Authors
Wei D, Le X, Zheng L, Wang L, Frey JA, Gao AC, Peng Z, Huang S, Xiong HQ, Abbruzzese JL, Xie K.
  Title
Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis.
  Journal
Oncogene 22:319-29 (2003)
Reference
  Authors
Toyonaga T, Nakano K, Nagano M, Zhao G, Yamaguchi K, Kuroki S, Eguchi T, Chijiiwa K, Tsuneyoshi M, Tanaka M.
  Title
Blockade of constitutively activated Janus kinase/signal transducer and activator of transcription-3 pathway inhibits growth of human pancreatic cancer.
  Journal
Cancer Lett 201:107-16 (2003)
Reference
  Authors
Schmid RM.
  Title
Genetic basis of pancreatic cancer.
  Journal
Best Pract Res Clin Gastroenterol 16:421-33 (2002)
Reference
  Authors
Elliott RL, Blobe GC.
  Title
Role of transforming growth factor Beta in human cancer.
  Journal
J Clin Oncol 23:2078-93 (2005)
Reference
  Authors
Rudkin TM, Foulkes WD.
  Title
BRCA2: breaks, mistakes and failed separations.
  Journal
Trends Mol Med 11:145-8 (2005)
Reference
  Authors
Venkitaraman AR.
  Title
Functions of BRCA1 and BRCA2 in the biological response to DNA damage.
  Journal
J Cell Sci 114:3591-8 (2001)
KO pathway
 

DBGET integrated database retrieval system