Entry Name Pancreatic cancer - Microcebus murinus (gray mouse lemur)
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 Microcebus murinus (gray mouse lemur) [GN:
mmur ]
Gene 105855026 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
105855821 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
105857966 SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605 ]
105859419 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
105859871 RALGDS; ral guanine nucleotide dissociation stimulator isoform X1 [KO:K08732 ]
105860538 SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500 ]
105862660 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
105866772 ARHGEF6; rho guanine nucleotide exchange factor 6 isoform X2 [KO:K05729 ]
105868254 RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
105872305 EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357 ]
105872856 GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402 ]
105873508 CHUK; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467 ] [EC:2.7.11.10 ]
105873610 CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393 ]
105873984 GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
105874233 SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501 ]
105874819 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
105876174 GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
105877483 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
105877906 STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220 ]
105878067 RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861 ]
105881219 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
105883746 RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860 ]
105886063 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
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
