Entry
Name
Pancreatic cancer - Arvicola amphibius (Eurasian water vole)
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; Cancer: specific types
BRITE hierarchy
Pathway map
Ortholog table
Organism
Arvicola amphibius (Eurasian water vole) [GN:
aamp ]
Gene
119816315 Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
119810503 Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
119826317 Pik3ca; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
119808979 Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
119817743 phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
119812102 Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
119805248 Arhgef6; LOW QUALITY PROTEIN: rho guanine nucleotide exchange factor 6 [KO:K05729 ]
119824999 Rac1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
119812100 Rac3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861 ]
119801102 Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
119820525 Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158 ]
119819393 Ralgds; ral guanine nucleotide dissociation stimulator isoform X1 [KO:K08732 ]
119811206 Stat3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
119803912 Stat1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220 ]
119822349 Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
119816942 Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma isoform X1 [KO:K04402 ]
119807493 Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402 ]
119821456 Tgfb1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375 ]
119827432 Tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376 ]
119825089 Brca2; LOW QUALITY PROTEIN: breast cancer type 2 susceptibility protein [KO:K08775 ]
Compound
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
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
Reference
Authors
Bardeesy N, Sharpless NE, DePinho RA, Merlino G.
Title
The genetics of pancreatic adenocarcinoma: a roadmap for a mouse model.
Journal
Reference
Authors
Cowgill SM, Muscarella P.
Title
The genetics of pancreatic cancer.
Journal
Reference
Authors
Hezel AF, Kimmelman AC, Stanger BZ, Bardeesy N, Depinho RA.
Title
Genetics and biology of pancreatic ductal adenocarcinoma.
Journal
Reference
Authors
Shields JM, Pruitt K, McFall A, Shaub A, Der CJ.
Title
Understanding Ras: 'it ain't over 'til it's over'.
Journal
Reference
Authors
Holbro T, Civenni G, Hynes NE.
Title
The ErbB receptors and their role in cancer progression.
Journal
Reference
Authors
Marmor MD, Skaria KB, Yarden Y.
Title
Signal transduction and oncogenesis by ErbB/HER receptors.
Journal
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
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
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
Reference
Authors
Schmid RM.
Title
Genetic basis of pancreatic cancer.
Journal
Reference
Authors
Elliott RL, Blobe GC.
Title
Role of transforming growth factor Beta in human cancer.
Journal
Reference
Authors
Rudkin TM, Foulkes WD.
Title
BRCA2: breaks, mistakes and failed separations.
Journal
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)
Reference
Authors
Chang Z, Li Z, Wang X, Kang Y, Yuan Y, Niu J, Wang H, Chatterjee D, Fleming JB, Li M, Abbruzzese JL, Chiao PJ
Title
Deciphering the mechanisms of tumorigenesis in human pancreatic ductal epithelial cells.
Journal
Related pathway
KO pathway
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