Entry Name Pancreatic cancer - Phascolarctos cinereus (koala)
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 typesBRITE hierarchy
Pathway map Ortholog table Organism Phascolarctos cinereus (koala) [GN:
pcw ]
Gene 110204454 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
110208219 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
110199476 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
110223395 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
110216530 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
110209293 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
110197717 ARHGEF6; rho guanine nucleotide exchange factor 6 isoform X1 [KO:K05729 ]
110193513 RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
110218260 RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861 ]
110209686 NFKB1; LOW QUALITY PROTEIN: nuclear factor NF-kappa-B p105 subunit [KO:K02580 ]
110195467 BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158 ]
110205393 RALGDS; ral guanine nucleotide dissociation stimulator isoform X1 [KO:K08732 ]
110206033 CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393 ]
110198372 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
110213248 STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220 ]
110217257 CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625 ]
110212964 GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402 ]
110223449 GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
110195907 GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
110223919 DDB2; LOW QUALITY PROTEIN: DNA damage-binding protein 2 [KO:K10140 ]
110205565 TGFB2; LOW QUALITY PROTEIN: transforming growth factor beta-2 [KO:K13376 ]
110207982 SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500 ]
110215556 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 KO pathway LinkDB All DBs
