Entry Name Pancreatic cancer - Ursus maritimus (polar bear)
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 Disease Organism Ursus maritimus (polar bear) [GN:
umr ]
Gene 103658194 TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376 ]
103659933 STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220 ]
103663135 GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402 ]
103663617 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649 ]
103663939 SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500 ]
103664148 VEGFA; LOW QUALITY PROTEIN: vascular endothelial growth factor A [KO:K05448 ]
103665536 CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625 ]
103666008 RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861 ]
103666874 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
103670397 RALGDS; ral guanine nucleotide dissociation stimulator isoform X1 [KO:K08732 ]
103670766 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
103672573 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
103672855 ARHGEF6; rho guanine nucleotide exchange factor 6 isoform X1 [KO:K05729 ]
103675162 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
103676125 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
103676407 RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860 ]
103677394 TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375 ]
103677947 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
103678592 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
103681651 GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
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
