Entry Name Pancreatic cancer - Mus musculus (house mouse)
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 Mus musculus (house mouse) [GN:
mmu ]
Gene 16653 Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827 ]
18706 Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
18707 Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
74769 Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
18709 Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
18708 Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
18710 Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
73341 Arhgef6; Rac/Cdc42 guanine nucleotide exchange factor 6 [KO:K05729 ]
18033 Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580 ]
19697 Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735 ]
16151 Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210 ]
12015 Bad; BCL2-associated agonist of cell death [KO:K02158 ]
19730 Ralgds; ral guanine nucleotide dissociation stimulator [KO:K08732 ]
56044 Rala; v-ral simian leukemia viral oncogene A (ras related) [KO:K07834 ]
64143 Ralb; v-ral simian leukemia viral oncogene B [KO:K07835 ]
21802 Tgfa; transforming growth factor alpha [KO:K08774 ]
20848 Stat3; signal transducer and activator of transcription 3 [KO:K04692 ]
20846 Stat1; signal transducer and activator of transcription 1 [KO:K11220 ]
22339 Vegfa; vascular endothelial growth factor A [KO:K05448 ]
12578 Cdkn2a; cyclin dependent kinase inhibitor 2A [KO:K06621 ]
19645 Rb1; RB transcriptional corepressor 1 [KO:K06618 ]
22059 Trp53; transformation related protein 53 [KO:K04451 ]
12575 Cdkn1a; cyclin dependent kinase inhibitor 1A [KO:K06625 ]
13197 Gadd45a; growth arrest and DNA-damage-inducible 45 alpha [KO:K04402 ]
17873 Gadd45b; growth arrest and DNA-damage-inducible 45 beta [KO:K04402 ]
23882 Gadd45g; growth arrest and DNA-damage-inducible 45 gamma [KO:K04402 ]
107986 Ddb2; damage specific DNA binding protein 2 [KO:K10140 ]
21803 Tgfb1; transforming growth factor, beta 1 [KO:K13375 ]
21808 Tgfb2; transforming growth factor, beta 2 [KO:K13376 ]
21809 Tgfb3; transforming growth factor, beta 3 [KO:K13377 ]
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
