KEGG PATHWAY: pon05212

PATHWAY: pon05212

Entry

pon05212 Pathway

Name

Pancreatic cancer - Pongo abelii (Sumatran orangutan)

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

pon05212

Pancreatic cancer

Organism

Pongo abelii (Sumatran orangutan) [GN:pon]

Gene

100462513	GTPase KRas-like; K07827 GTPase KRas [KO:K07827]
100432846	PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
100453085	PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
100453779	PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
100174298	PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
100455593	PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
100173589	PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
100189665	DKFZP459B1536 protein; K02649 phosphoinositide-3-kinase, regulatory subunit [KO:K02649]
100437617	PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
100434767	ARHGEF6; Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6 [KO:K05729]
100443271	RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
100936711	rho-related protein rac1B-like; K04392 Ras-related C3 botulinum toxin substrate 1 [KO:K04392]
100431483	RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
100456212	RAC3; ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) [KO:K07861]
100461595	NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
100456049	RELA; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
100454279	AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
100448114	AKT3; v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma) [KO:K04456] [EC:2.7.11.1]
100174735	CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
100440586	IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
100449496	IKBKG; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
100454097	BAD; BCL2-associated agonist of cell death [KO:K02158]
100453051	BCL2L1; BCL2-like 1 [KO:K04570]
100460459	CASP9; caspase 9, apoptosis-related cysteine peptidase [KO:K04399] [EC:3.4.22.62]
100431871	ARAF; v-raf murine sarcoma 3611 viral oncogene homolog [KO:K08845] [EC:2.7.11.1]
100442288	BRAF; v-raf murine sarcoma viral oncogene homolog B1 [KO:K04365] [EC:2.7.11.1]
100173732	RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [KO:K04366] [EC:2.7.11.1]
100446021	MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100431824	MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100169740	MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100174482	MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
100459133	MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
100437424	MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
100451493	RALGDS; ral guanine nucleotide dissociation stimulator [KO:K08732]
100441438	RALA; v-ral simian leukemia viral oncogene homolog A (ras related) [KO:K07834]
100174018	RALB; v-ral simian leukemia viral oncogene homolog B (ras related [KO:K07835]
100431225	RALBP1; ralA binding protein 1 [KO:K08773]
100438199	CDC42; cell division cycle 42 (GTP binding protein, 25kDa) [KO:K04393]
100172994	TGFA; transforming growth factor, alpha [KO:K08774]
100455021	EGF; epidermal growth factor [KO:K04357]
100459280	EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
100450307	ERBB2; v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) [KO:K05083] [EC:2.7.10.1]
100433477	JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
100171541	STAT3; signal transducer and activator of transcription 3 (acute-phase response factor) [KO:K04692]
100173683	STAT1; signal transducer and activator of transcription 1, 91kDa [KO:K11220]
100448769	uncharacterized LOC100448769; K05448 vascular endothelial growth factor A [KO:K05448]
100461015	cyclin-dependent kinase inhibitor 2A; K06621 cyclin-dependent kinase inhibitor 2A [KO:K06621]
100443314	CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
100454924	CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
100171625	CCND1; cyclin D1 [KO:K04503]
100462155	RB1; retinoblastoma 1 [KO:K06618]
100448297	E2F3; E2F transcription factor 3 [KO:K06620]
100435851	E2F1; E2F transcription factor 1 [KO:K06620]
100458002	E2F2; E2F transcription factor 2 [KO:K09389]
100435218	TP53; tumor protein p53 [KO:K04451]
100459982	TGFB1; transforming growth factor, beta 1 [KO:K13375]
100461291	TGFB2; transforming growth factor, beta 2 [KO:K13376]
100433208	TGFB3; transforming growth factor, beta 3 [KO:K13377]
100450864	TGFBR1; transforming growth factor, beta receptor 1 [KO:K04674] [EC:2.7.11.30]
100459236	TGFBR2; transforming growth factor, beta receptor II (70/80kDa) [KO:K04388] [EC:2.7.11.30]
100448249	SMAD3; SMAD family member 3 [KO:K04500]
100173357	SMAD2; SMAD family member 2 [KO:K04500]
100439171	SMAD4; SMAD family member 4 [KO:K04501]
100435800	BRCA2; breast cancer 2, early onset [KO:K08775]
100432066	RAD51; RAD51 homolog (S. cerevisiae) [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 (65)   
   KEGG GENES (65)   
All databases (67)   

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