KEGG   PATHWAY: ko05212Help
Entry
ko05212                     Pathway                                

Name
Pancreatic cancer
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
ko05212

All organismsOrtholog table
Disease
H00019  
Pancreatic cancer
Orthology
K07827  
GTPase KRas
K00922  
phosphatidylinositol-4,5-bisphosphate 3-kinase [EC:2.7.1.153]
K02649  
phosphoinositide-3-kinase, regulatory subunit
K05729  
Rho guanine nucleotide exchange factor 6
K04392  
Ras-related C3 botulinum toxin substrate 1
K07860  
Ras-related C3 botulinum toxin substrate 2
K07861  
Ras-related C3 botulinum toxin substrate 3
K02580  
nuclear factor NF-kappa-B p105 subunit
K04735  
transcription factor p65
K04456  
RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04467  
inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K07209  
inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K07210  
inhibitor of nuclear factor kappa-B kinase subunit gamma
K02158  
BCL2-antagonist of cell death
K04570  
BCL2-like 1 (apoptosis regulator Bcl-X)
K04399  
caspase 9 [EC:3.4.22.62]
K08845  
A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04365  
B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  
RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  
mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04371  
mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04440  
c-Jun N-terminal kinase [EC:2.7.11.24]
K08732  
ral guanine nucleotide dissociation stimulator
K07834  
Ras-related protein Ral-A
K07835  
Ras-related protein Ral-B
K08773  
RalA-binding protein 1
K04393  
cell division control protein 42
K08774  
transforming growth factor, alpha
K04357  
epidermal growth factor
K04361  
epidermal growth factor receptor [EC:2.7.10.1]
K05083  
receptor tyrosine-protein kinase erbB-2 [EC:2.7.10.1]
K11217  
Janus kinase 1 [EC:2.7.10.2]
K04692  
signal transducer and activator of transcription 3
K11220  
signal transducer and activator of transcription 1
K05448  
vascular endothelial growth factor A
K06621  
cyclin-dependent kinase inhibitor 2A
K02089  
cyclin-dependent kinase 4 [EC:2.7.11.22]
K02091  
cyclin-dependent kinase 6 [EC:2.7.11.22]
K04503  
cyclin D1
K06618  
retinoblastoma-associated protein
K17454  
transcription factor E2F1
K09389  
transcription factor E2F2
K06620  
transcription factor E2F3
K04451  
tumor protein p53
K13375  
transforming growth factor beta-1
K13376  
transforming growth factor beta-2
K13377  
transforming growth factor beta-3
K04674  
TGF-beta receptor type-1 [EC:2.7.11.30]
K04388  
TGF-beta receptor type-2 [EC:2.7.11.30]
K04500  
mothers against decapentaplegic homolog 2/3
K04501  
mothers against decapentaplegic homolog 4
K08775  
breast cancer 2 susceptibility protein
K04482  
DNA repair protein RAD51
Compound
C00416  
Phosphatidate
C05981  
Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
  Title
  Journal
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)

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