KEGG PATHWAY: oaa05212

PATHWAY: oaa05212

Entry

oaa05212 Pathway

Name

Pancreatic cancer - Ornithorhynchus anatinus (platypus)

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; Cancers

Pathway map

oaa05212

Pancreatic cancer

Organism

Ornithorhynchus anatinus (platypus) [GN:oaa]

Gene

100085430	GTPase KRas-like; K07827 GTPase KRas [KO:K07827]
100086270	PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
100073788	phosphatidylinositol-4; K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase [EC:2.7.1.153] [KO:K00922] [EC:2.7.1.153]
100078046	phosphatidylinositol-4; K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase [EC:2.7.1.153] [KO:K00922] [EC:2.7.1.153]
100084050	phosphoinositide 3-kinase regulatory subunit 5-like; K02649 phosphoinositide-3-kinase, regulatory subunit [KO:K02649]
100080187	PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
100084726	phosphatidylinositol 3-kinase regulatory subunit alpha-like; K02649 phosphoinositide-3-kinase, regulatory subunit [KO:K02649]
100082075	phosphatidylinositol 3-kinase regulatory subunit gamma-like; K02649 phosphoinositide-3-kinase, regulatory subunit [KO:K02649]
100083576	ARHGEF6; Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6 [KO:K05729]
100076220	ras-related C3 botulinum toxin substrate 1-like; K04392 Ras-related C3 botulinum toxin substrate 1 [KO:K04392]
100092844	ras-related C3 botulinum toxin substrate 2-like; K07860 Ras-related C3 botulinum toxin substrate 2 [KO:K07860]
100083819	nuclear factor NF-kappa-B p105 subunit-like; K02580 nuclear factor NF-kappa-B p105 subunit [KO:K02580]
100081469	nuclear factor NF-kappa-B p105 subunit-like; K02580 nuclear factor NF-kappa-B p105 subunit [KO:K02580]
100074633	transcription factor p65-like; K04735 transcription factor p65 [KO:K04735]
100083320	RAC-gamma serine/threonine-protein kinase-like; K04456 RAC serine/threonine-protein kinase [EC:2.7.11.1] [KO:K04456] [EC:2.7.11.1]
100081473	RAC-alpha serine/threonine-protein kinase-like; K04456 RAC serine/threonine-protein kinase [EC:2.7.11.1] [KO:K04456] [EC:2.7.11.1]
100082351	CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
100078925	IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
100073613	NF-kappa-B essential modulator-like; K07210 inhibitor of nuclear factor kappa-B kinase subunit gamma [KO:K07210]
100092345	caspase-9-like; K04399 caspase 9 [EC:3.4.22.62] [KO:K04399] [EC:3.4.22.62]
100084423	serine/threonine-protein kinase A-Raf-like; K08845 A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1] [KO:K08845] [EC:2.7.11.1]
100086380	serine/threonine-protein kinase B-raf-like; K04365 B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1] [KO:K04365] [EC:2.7.11.1]
100089456	RAF proto-oncogene serine/threonine-protein kinase-like; K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1] [KO:K04366] [EC:2.7.11.1]
100080362	dual specificity mitogen-activated protein kinase kinase 1-like; K04368 mitogen-activated protein kinase kinase 1 [EC:2.7.12.2] [KO:K04368] [EC:2.7.12.2]
100085480	mitogen-activated protein kinase 1-like; K04371 extracellular signal-regulated kinase 1/2 [EC:2.7.11.24] [KO:K04371] [EC:2.7.11.24]
100073424	MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
100076033	MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
100082590	uncharacterized LOC100082590; K04440 c-Jun N-terminal kinase [EC:2.7.11.24] [KO:K04440] [EC:2.7.11.24]
100080818	ral guanine nucleotide dissociation stimulator-like; K08732 ral guanine nucleotide dissociation stimulator [KO:K08732]
100075904	ras-related protein Ral-A-like; K07834 Ras-related protein Ral-A [KO:K07834]
100087330	ras-related protein ralB-B-like; K07835 Ras-related protein Ral-B [KO:K07835]
100081456	RALBP1; ralA binding protein 1 [KO:K08773]
100086186	cell division control protein 42 homolog; K04393 cell division control protein 42 [KO:K04393]
100090413	protransforming growth factor alpha-like; K08774 transforming growth factor, alpha [KO:K08774]
100075894	EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
100087266	signal transducer and activator of transcription 1-like; K11220 signal transducer and activator of transcription 1 [KO:K11220]
100077009	vascular endothelial growth factor A-like; K05448 vascular endothelial growth factor A [KO:K05448]
100083932	cyclin-dependent kinase inhibitor 2A; K06621 cyclin-dependent kinase inhibitor 2A [KO:K06621]
100091822	cyclin-dependent kinase 6-like; K02091 cyclin-dependent kinase 6 [EC:2.7.11.22] [KO:K02091] [EC:2.7.11.22]
100075081	G1/S-specific cyclin-D1-like; K04503 cyclin D1 [KO:K04503]
100083537	RB1; retinoblastoma 1 [KO:K06618]
100090475	transcription factor E2F3-like; K06620 E2F transcription factor 1/3 [KO:K06620]
100085053	transcription factor E2F2-like; K09389 E2F transcription factor 2 [KO:K09389]
100080176	transforming growth factor beta-2-like; K13376 transforming growth factor beta-2 [KO:K13376]
100074840	transforming growth factor beta-3-like; K13377 transforming growth factor beta-3 [KO:K13377]
100092358	TGF-beta receptor type-1-like; K04674 TGF-beta receptor type-1 [EC:2.7.11.30] [KO:K04674] [EC:2.7.11.30]
100076965	TGFBR2; transforming growth factor, beta receptor II (70/80kDa) [KO:K04388] [EC:2.7.11.30]
100073364	SMAD2; SMAD family member 2 [KO:K04500]
100077136	mothers against decapentaplegic homolog 4-like; K04501 mothers against decapentaplegic homolog 4 [KO:K04501]
100079887	BRCA2; breast cancer 2, early onset [KO:K08775]
100081320	DNA repair protein RAD51 homolog 1-like; K04482 DNA repair protein RAD51 [KO:K04482]
100091144	DNA repair protein RAD51 homolog 1-like; K04482 DNA repair protein RAD51 [KO:K04482]

Compound

C00416	Phosphatidate
C05981	Phosphatidylinositol-3,4,5-trisphosphate

Reference

Authors

Von Hoff DD, Evans DB, Hruban RH (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

PMID:12459728

Authors

Bardeesy N, DePinho RA.

Title

Pancreatic cancer biology and genetics.

Journal

Nat Rev Cancer 2:897-909 (2002)

Reference

PMID:11407945

Authors

Bardeesy N, Sharpless NE, DePinho RA, Merlino G.

Title

The genetics of pancreatic adenocarcinoma: a roadmap for a mouse model.

Journal

Semin Cancer Biol 11:201-18 (2001)

Reference

PMID:12946833

Authors

Cowgill SM, Muscarella P.

Title

The genetics of pancreatic cancer.

Journal

Am J Surg 186:279-86 (2003)

Reference

PMID:16702400

Authors

Hezel AF, Kimmelman AC, Stanger BZ, Bardeesy N, Depinho RA.

Title

Genetics and biology of pancreatic ductal adenocarcinoma.

Journal

Genes Dev 20:1218-49 (2006)

Reference

PMID:10740269

Authors

Shields JM, Pruitt K, McFall A, Shaub A, Der CJ.

Title

Understanding Ras: 'it ain't over 'til it's over'.

Journal

Trends Cell Biol 10:147-54 (2000)

Reference

PMID:12648469

Authors

Holbro T, Civenni G, Hynes NE.

Title

The ErbB receptors and their role in cancer progression.

Journal

Exp Cell Res 284:99-110 (2003)

Reference

PMID:14967450

Authors

Marmor MD, Skaria KB, Yarden Y.

Title

Signal transduction and oncogenesis by ErbB/HER receptors.

Journal

Int J Radiat Oncol Biol Phys 58:903-13 (2004)

Reference

PMID:14586404

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

Oncogene 22:7781-95 (2003)

Reference

PMID:12545153

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

Oncogene 22:319-29 (2003)

Reference

PMID:14580692

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

Cancer Lett 201:107-16 (2003)

Reference

PMID:12079267

Authors

Schmid RM.

Title

Genetic basis of pancreatic cancer.

Journal

Best Pract Res Clin Gastroenterol 16:421-33 (2002)

Reference

PMID:15774796

Authors

Elliott RL, Blobe GC.

Title

Role of transforming growth factor Beta in human cancer.

Journal

J Clin Oncol 23:2078-93 (2005)

Reference

PMID:15823750

Authors

Rudkin TM, Foulkes WD.

Title

BRCA2: breaks, mistakes and failed separations.

Journal

Trends Mol Med 11:145-8 (2005)

Reference

PMID:11707511

Authors

Venkitaraman AR.

Title

Functions of BRCA1 and BRCA2 in the biological response to DNA damage.

Journal

J Cell Sci 114:3591-8 (2001)

KO pathway

ko05212

All links

Pathway (1)   
   BioSystems (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (52)   
   KEGG GENES (52)   
All databases (54)   

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