Entry |
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Name |
Pancreatic cancer - Homo sapiens (human)
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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.
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Class |
Human Diseases; Cancer: specific types
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Pathway map |

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Network |
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Element |
N00012 | Mutation-activated KRAS/NRAS to ERK signaling pathway |
N00032 | Mutation-activated KRAS/NRAS to PI3K signaling pathway |
N00034 | ERBB2-overexpression to PI3K signaling pathway |
N00070 | Mutation-inactivated p16(INK4a) to p16-cell cycle G1/S |
N00071 | Deleted p16(INK4a) to p16-cell cycle G1/S |
N00095 | ERBB2-overexpression to EGF-Jak-STAT signaling pathway |
N00104 | Mutation-activated KRAS to RalGDS signaling pathway |
N00115 | Mutation-inactivated TP53 to transcription |
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Disease |
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Drug |
D04023 | Erlotinib hydrochloride (JAN/USAN) |
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Organism |
Homo sapiens (human) [GN: hsa]
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Gene |
3845 | KRAS; KRAS proto-oncogene, GTPase [KO:K07827] |
5290 | PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153] |
5293 | PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153] |
5291 | PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153] |
5295 | PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649] |
5296 | PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649] |
8503 | PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649] |
9459 | ARHGEF6; Rac/Cdc42 guanine nucleotide exchange factor 6 [KO:K05729] |
4790 | NFKB1; nuclear factor kappa B subunit 1 [KO:K02580] |
5970 | RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735] |
1147 | CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:2.7.11.10] |
8517 | IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210] |
572 | BAD; BCL2 associated agonist of cell death [KO:K02158] |
5900 | RALGDS; ral guanine nucleotide dissociation stimulator [KO:K08732] |
998 | CDC42; cell division cycle 42 [KO:K04393] |
7039 | TGFA; transforming growth factor alpha [KO:K08774] |
6774 | STAT3; signal transducer and activator of transcription 3 [KO:K04692] |
6772 | STAT1; signal transducer and activator of transcription 1 [KO:K11220] |
7422 | VEGFA; vascular endothelial growth factor A [KO:K05448] |
1029 | CDKN2A; cyclin dependent kinase inhibitor 2A [KO:K06621] |
5925 | RB1; RB transcriptional corepressor 1 [KO:K06618] |
1026 | CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625] |
1647 | GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402] |
4616 | GADD45B; growth arrest and DNA damage inducible beta [KO:K04402] |
10912 | GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402] |
581 | BAX; BCL2 associated X, apoptosis regulator [KO:K02159] |
578 | BAK1; BCL2 antagonist/killer 1 [KO:K14021] |
1643 | DDB2; damage specific DNA binding protein 2 [KO:K10140] |
7040 | TGFB1; transforming growth factor beta 1 [KO:K13375] |
7042 | TGFB2; transforming growth factor beta 2 [KO:K13376] |
7043 | TGFB3; transforming growth factor beta 3 [KO:K13377] |
675 | BRCA2; BRCA2 DNA repair associated [KO:K08775] |
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Compound |
C05981 | Phosphatidylinositol-3,4,5-trisphosphate |
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Reference |
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Authors |
Von Hoff D, Evans D, Hruban R (ed). |
Title |
Pancreatic cancer |
Journal |
Jones and Bartlett publishers (2005) |
Reference |
(Japanese) |
Authors |
Niitsu Y, Yokota J (ed). |
Title |
[Oncogenes and Tumor Suppressor Genes for Medical Oncologist] (In Japanese) |
Journal |
Nankodo (1999) |
Reference |
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Authors |
Bardeesy N, DePinho RA. |
Title |
Pancreatic cancer biology and genetics. |
Journal |
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Reference |
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Authors |
Bardeesy N, Sharpless NE, DePinho RA, Merlino G. |
Title |
The genetics of pancreatic adenocarcinoma: a roadmap for a mouse model. |
Journal |
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Reference |
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Authors |
Cowgill SM, Muscarella P. |
Title |
The genetics of pancreatic cancer. |
Journal |
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Reference |
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Authors |
Hezel AF, Kimmelman AC, Stanger BZ, Bardeesy N, Depinho RA. |
Title |
Genetics and biology of pancreatic ductal adenocarcinoma. |
Journal |
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Reference |
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Authors |
Shields JM, Pruitt K, McFall A, Shaub A, Der CJ. |
Title |
Understanding Ras: 'it ain't over 'til it's over'. |
Journal |
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Reference |
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Authors |
Holbro T, Civenni G, Hynes NE. |
Title |
The ErbB receptors and their role in cancer progression. |
Journal |
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Reference |
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Authors |
Marmor MD, Skaria KB, Yarden Y. |
Title |
Signal transduction and oncogenesis by ErbB/HER receptors. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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Authors |
Schmid RM. |
Title |
Genetic basis of pancreatic cancer. |
Journal |
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Reference |
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Authors |
Elliott RL, Blobe GC. |
Title |
Role of transforming growth factor Beta in human cancer. |
Journal |
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Reference |
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Authors |
Rudkin TM, Foulkes WD. |
Title |
BRCA2: breaks, mistakes and failed separations. |
Journal |
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Reference |
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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 |
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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 |
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Related pathway |
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KO pathway |
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LinkDB |
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