Androgen Receptor Network in Prostate Cancer (Homo sapiens)

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SWI/SNF Apoptotic Pathways MIR21 MYC_HUMAN MIR21 FOXA1 TRANSLATION SPINK1 FKBP5 SPINK1 TSC1_HUMAN SPRY1 AR AR * 3-beta-OH-delta-steroid DH & Steroid isomerase = * ** Estradiol-17-beta DH = DHB ** HSD17B7 HSD17B4 HSD17B2 HSD17B3 HSD17B1 * HSD3B1 HSD3B2 HSD3B1 HSD3B1 HSD3B1 HSD3B1 * HSD3B1 HSD3B1 HSD3B1 HSD3B2 HSD3B1 HSD3B1 HSD3B2 HSD3B1 HSD3B1 HSD3B1 HSD3B1 HSD3B1 CYP17A1 17-alpha-OH-Progesterone Dihydrotestosterone HSD3B1 HSD3B1 HSD3B1 HSD3B1 HSD3B2 HSD3B1 Androstenedione Hydroxyprogesterone aldolase Progesterone Estradiol Testosterone Estrone HSD3B1 Androstenediol F13B Glucocortocoid Synthesis dehydroepiandrosterone Hydroxyprogesterone aldolase Steroid-19-Hydroxylase Pregnenolone CYP17A1 17-alpha-OH-Pregnenolone Cholesterol Mineralocortocoid Synthesis Steroid-19-Hydroxylase BASC Comlex RAD50_HUMAN OCT1 MSH6_HUMAN p14 CDC2_HUMAN p38 ATF1 ARID1A ASK1 BRCA1_HUMAN CASP8_HUMAN PLK1 ATR_HUMAN BARD1_HUMAN CASP9_HUMAN CDC25B PUMA RB_HUMAN SMAD3_HUMAN NOXA1_HUMAN BLM_HUMAN Q8NBS1_HUMAN CDK4_HUMAN MRE11_HUMAN STAT1_HUMAN CDC25A BCL2_HUMAN AKT1_HUMAN CASP3_HUMAN BACH1 P53_HUMAN CHK2_HUMAN p15 JAK1_HUMAN p27 MSH2_HUMAN BAX_HUMAN p13K PRKDC_HUMAN CHK1_HUMAN BRCA1_HUMAN MMP1_HUMAN CDK2_HUMAN BAD_HUMAN ATM_HUMAN SMAD2_HUMAN E2F1_HUMAN MDM2_HUMAN p21 TMPRSS2 KLK3 KLK2 NDRG1 ABCC4 TMPRSS2 ERG TMPRSS2 ETV4 SP1 ARID1B SMARCA4 SMARCC1 SMARCC2 SMARCD1 SMARCD2 SMARCD3 ACTL6A ACTL6B CDC42 pathway Trancription P RHO pathway Transcription of Cox2 AP-1 Transcription Anoikis Changes in Cytoskeleton and Cell mobility RAC1 pathway AKT Pathway MAP2K1 MAP2K2 MAP4K1 STAT3 HGF RAP1A RAP1B PTPN11 PTEN MAPK1 MAPK3 CRKL HRAS FOS JUN DOCK1 PXN RAPGEF1 RAF1 SOS1 Met PTK2B PIK3CA PAK1 ELK1 MAPK8 CRK GAB1 RASA1 GRB2 TSC2_HUMAN RHEB_HUMAN MTOR_HUMAN RICTOR RPTOR_HUMAN RPTOR_HUMAN 4EBP1_HUMAN MYC EIF4EBP1 EIF4E1B CCND1_HUMAN SPRY2 Name: Androgen Receptor Network in Prostate Cancer Organism: Homo sapiens


Description

The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding either of the androgenic hormones, testosterone, or dihydrotestosterone in the cytoplasm and then translocating into the nucleus. The main function of the androgen receptor is as a DNA-binding transcription factor that regulates gene expression. The AR is important for therapeutic target in prostate cancer, thus many different inhibitors have been developed, primarily targeting the ligand binding domain of the protein, while inhibitors that target the N-terminal domain of the protein are still under development. Description source: Wikipedia

Quality Tags

Ontology Terms

<OntologyTags></OntologyTags>

Bibliography

  1. Tomlins SA, Rhodes DR, Yu J, Varambally S, Mehra R, Perner S, Demichelis F, Helgeson BE, Laxman B, Morris DS, Cao Q, Cao X, Andrén O, Fall K, Johnson L, Wei JT, Shah RB, Al-Ahmadie H, Eastham JA, Eggener SE, Fine SW, Hotakainen K, Stenman UH, Tsodikov A, Gerald WL, Lilja H, Reuter VE, Kantoff PW, Scardino PT, Rubin MA, Bjartell AS, Chinnaiyan AM; ''The role of SPINK1 in ETS rearrangement-negative prostate cancers.''; Cancer Cell, 2008 PubMed
  2. Schramedei K, Mörbt N, Pfeifer G, Läuter J, Rosolowski M, Tomm JM, von Bergen M, Horn F, Brocke-Heidrich K; ''MicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4.''; Oncogene, 2011 PubMed
  3. Liu LZ, Li C, Chen Q, Jing Y, Carpenter R, Jiang Y, Kung HF, Lai L, Jiang BH; ''MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1α expression.''; PLoS One, 2011 PubMed

History

View all...
RevisionActionTimeUserComment
96290view 08:39, 7 March 2018Fehrhartconnected lines-replace by graphic item
96015view 08:04, 15 February 2018MkutmonModified description
96014view 08:03, 15 February 2018MkutmonModified description
96013view 08:00, 15 February 2018MkutmonModified title
85556view 01:33, 29 May 2016EgonwReplaced a mim-conversion with Arrow.
84985view 11:49, 4 April 2016AlexanderPicoreplaced mim-conversion with mim-transcription-translation for gene to protein
80439view 13:55, 22 June 2015KhanspersAdded mir21 targeting of SMARCA4
80426view 11:58, 22 June 2015KhanspersAdded mir21 targeting of PTEN and connected interactions
79838view 00:57, 18 April 2015EgonwFixed the metabolite label.
79823view 00:44, 17 April 2015EgonwReplaced "EC Number" with "Enzyme Nomenclature" as data source (fixing the links out).
73838view 17:09, 25 February 2014MaintBotupdated schema
71495view 12:19, 17 October 2013MaintBotUpdated data sources
69730view 01:23, 11 July 2013EgonwHydroxyprogesterone aldolase is not a metabolite.
67609view 04:32, 26 June 2013DdiglesOntology Term : 'prostate cancer pathway' added !
59165view 11:25, 22 February 2013MaintBotUpdated Ensembl data source
54728view 12:59, 7 December 2012MaintBotadded p38
54672view 14:25, 6 December 2012RobertbaertschPeriodical save, work in progress
54277view 13:35, 26 November 2012RobertbaertschPeriodical save, work in progress
54276view 13:15, 26 November 2012RobertbaertschPeriodical save, work in progress
54275view 12:39, 26 November 2012RobertbaertschPeriodical save, work in progress
54241view 01:35, 24 November 2012RobertbaertschPeriodical save, work in progress
53136view 18:55, 29 October 2012MaintBotModified categories
50365view 15:16, 13 August 2012PgfebboOntology Term : 'prostate cancer' added !
50348view 23:01, 12 August 2012Pgfebbomore changes
50347view 22:55, 12 August 2012PgfebboPeriodical save, work in progress
50346view 22:45, 12 August 2012PgfebboPeriodical save, work in progress
50345view 22:35, 12 August 2012PgfebboPeriodical save, work in progress
50344view 22:33, 12 August 2012PgfebboMTOR PATHWAY
50302view 07:43, 12 August 2012PgfebboPeriodical save, work in progress
50301view 07:33, 12 August 2012PgfebboPeriodical save, work in progress
50300view 07:18, 12 August 2012PgfebboAdded SPINK1
50269view 23:52, 10 August 2012Pgfebbofurther refinement
50268view 23:52, 10 August 2012PgfebboPeriodical save, work in progress
50267view 23:44, 10 August 2012PgfebboMORE EDITS
50266view 23:41, 10 August 2012PgfebboPeriodical save, work in progress
50265view 23:31, 10 August 2012PgfebboPeriodical save, work in progress
50264view 23:21, 10 August 2012PgfebboPeriodical save, work in progress
50263view 23:08, 10 August 2012PgfebboREVISIONS
50262view 23:03, 10 August 2012PgfebboPeriodical save, work in progress
50261view 22:53, 10 August 2012PgfebboPeriodical save, work in progress
50260view 22:43, 10 August 2012PgfebboPeriodical save, work in progress
50259view 22:33, 10 August 2012PgfebboPeriodical save, work in progress
50258view 22:21, 10 August 2012PgfebboTmprss2 added
50257view 22:18, 10 August 2012Pgfebboar to hugo
50075view 16:42, 6 August 2012Pgfebborenamed
50073view 16:39, 6 August 2012Pgfebbointegrated cancer pathways added
50070view 16:34, 6 August 2012PgfebboAdded integrated cancer pathways
50069view 16:24, 6 August 2012Pgfebbotrying to add TP53
50062view 13:34, 6 August 2012Pgfebbodenovo androgen synthesis
50061view 13:23, 6 August 2012Pgfebboannotations

External references

DataNodes

View all...
NameTypeDatabase referenceComment
17-alpha-OH-PregnenoloneMetaboliteHMDB00363 (HMDB)
17-alpha-OH-ProgesteroneMetaboliteHMDB00374 (HMDB)
4EBP1_HUMANProteinQ13541 (Uniprot-TrEMBL)
ABCC4GeneProduct10257 (Entrez Gene)
ACTL6AGeneProduct86 (Entrez Gene)
ACTL6BGeneProduct51412 (Entrez Gene)
AKT1_HUMANProteinP31749 (Uniprot-TrEMBL)
ARProtein367 (Entrez Gene)AR
ARID1AGeneProduct8289 (Entrez Gene)
ARID1BGeneProduct57492 (Entrez Gene)
ASK1Protein
ATF1GeneProduct466 (Entrez Gene)
ATM_HUMANProteinQ13315 (Uniprot-TrEMBL)
ATR_HUMANProteinQ13535 (Uniprot-TrEMBL)
AndrostenediolMetaboliteHMDB05849 (HMDB)
AndrostenedioneMetabolite63-05-8 (CAS)
BACH1Protein
BAD_HUMANProteinQ92934 (Uniprot-TrEMBL)
BARD1_HUMANProteinQ99728 (Uniprot-TrEMBL)
BAX_HUMANProteinQ07812 (Uniprot-TrEMBL)
BCL2_HUMANProteinP10415 (Uniprot-TrEMBL)
BLM_HUMANProteinP54132 (Uniprot-TrEMBL)
BRCA1_HUMANProteinP38398 (Uniprot-TrEMBL)
CASP3_HUMANProteinP42574 (Uniprot-TrEMBL)
CASP8_HUMANProteinQ14790 (Uniprot-TrEMBL)
CASP9_HUMANProteinP55211 (Uniprot-TrEMBL)
CCND1_HUMANProteinP24385 (Uniprot-TrEMBL)
CDC25AGeneProductENSG00000164045 (Ensembl)
CDC25BGeneProductENSG00000101224 (Ensembl)
CDC2_HUMANProteinP06493 (Uniprot-TrEMBL)Oncogene
CDK2_HUMANProteinP24941 (Uniprot-TrEMBL)
CDK4_HUMANProteinP11802 (Uniprot-TrEMBL)
CHK1_HUMANProteinO14757 (Uniprot-TrEMBL)
CHK2_HUMANProteinO96017 (Uniprot-TrEMBL)Phosphrylated
CRKGeneProduct1398 (Entrez Gene)
CRKLGeneProduct1399 (Entrez Gene)
CYP17A1GeneProduct1586 (Entrez Gene)
CholesterolMetabolite57-88-5 (CAS)
DOCK1GeneProduct1793 (Entrez Gene)Interim Symbol: Dock1 predicted and Name: dedicator of cyto-kinesis 1 (predicted)
DihydrotestosteroneMetaboliteHMDB02961 (HMDB)
E2F1_HUMANProteinQ01094 (Uniprot-TrEMBL)
EIF4E1BProteinA6NMX2 (Uniprot-TrEMBL)
EIF4EBP1GeneProduct1978 (Entrez Gene)
  • From Entrez Gene: The protein encoded by this gene is a trypsin inhibitor, which is secreted from pancreatic acinar cells into pancreatic juice. It is thought to function in the prevention of trypsin-catalyzed premature activation of zymogens within the pancreas and the pancreatic duct. Mutations in this gene are associated with hereditary pancreatitis and tropical calcific pancreatitis
  • Association with Prostate Cancer - Chinnaiyan Lab Cancer Cell Paper - ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers (∼10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers.
ELK1GeneProduct2002 (Entrez Gene)
ERGGeneProduct2078 (Entrez Gene)Fusion partner with TMPRSS2 in about 40% of prostate cancers
ETV4GeneProduct2118 (Entrez Gene)Fusion partner with TMPRSS2 in about 40% of prostate cancers
EstradiolMetabolite57-91-0 (CAS)
EstroneMetabolite53-16-7 (CAS)
F13BGeneProduct2165 (Entrez Gene)
FKBP5Protein2289 (Entrez Gene)
FOSGeneProduct2353 (Entrez Gene)
FOXA1Protein3169 (Entrez Gene)DNA licensing factor for AR. Frequently occupies regions in enhancers with DNA recognition elements close to AR ARE
GAB1GeneProduct2549 (Entrez Gene)
GRB2GeneProduct2885 (Entrez Gene)
Glucocortocoid SynthesisPathwayWP237 (WikiPathways)
HGFGeneProduct3082 (Entrez Gene)
HRASGeneProduct3265 (Entrez Gene)
HSD17B1GeneProduct3292 (Entrez Gene)
HSD17B2GeneProduct3294 (Entrez Gene)
HSD17B3GeneProduct3293 (Entrez Gene)
HSD17B4GeneProduct3295 (Entrez Gene)
HSD17B7GeneProduct51478 (Entrez Gene)
HSD3B1GeneProduct3283 (Entrez Gene)
HSD3B2GeneProduct3284 (Entrez Gene)
Hydroxyprogesterone aldolaseGeneProduct4.1.2.30 (Enzyme Nomenclature)
JAK1_HUMANProteinP23458 (Uniprot-TrEMBL)
JUNGeneProduct3725 (Entrez Gene)
KLK2GeneProduct3817 (Entrez Gene)
KLK3GeneProduct354 (Entrez Gene)
MAP2K1GeneProduct5604 (Entrez Gene)
MAP2K2GeneProduct5605 (Entrez Gene)
MAP4K1GeneProduct11184 (Entrez Gene)
MAPK1GeneProduct5594 (Entrez Gene)
MAPK3GeneProduct5595 (Entrez Gene)
MAPK8GeneProduct5599 (Entrez Gene)
MDM2_HUMANProteinQ00987 (Uniprot-TrEMBL)Oncogene
MIR21RnaENSG00000199004 (Ensembl)
MMP1_HUMANProteinP03956 (Uniprot-TrEMBL)
MRE11_HUMANProteinP49959 (Uniprot-TrEMBL)
MSH2_HUMANProteinP43246 (Uniprot-TrEMBL)
MSH6_HUMANProteinP52701 (Uniprot-TrEMBL)
MTOR_HUMANProteinP42345 (Uniprot-TrEMBL)
MYCGeneProduct4609 (Entrez Gene)
MYC_HUMANProteinP01106 (Uniprot-TrEMBL)
MetGeneProduct24553 (Entrez Gene)
Mineralocortocoid SynthesisPathwayWP237 (WikiPathways)
NDRG1GeneProduct10397 (Entrez Gene)
NOXA1_HUMANProteinQ86UR1 (Uniprot-TrEMBL)
OCT1Protein
P53_HUMANProteinP04637 (Uniprot-TrEMBL)
PAK1GeneProduct5058 (Entrez Gene)
PIK3CAGeneProduct5290 (Entrez Gene)
PLK1GeneProductENSG00000166851 (Ensembl)
PRKDC_HUMANProteinP78527 (Uniprot-TrEMBL)
PTENGeneProduct5728 (Entrez Gene)
PTK2BGeneProduct2185 (Entrez Gene)
PTPN11GeneProduct5781 (Entrez Gene)
PUMAProtein
PXNGeneProduct5829 (Entrez Gene)
PregnenoloneMetabolite145-13-1 (CAS)
ProgesteroneMetabolite57-83-0 (CAS)
Q8NBS1_HUMANProteinQ8NBS1 (Uniprot-TrEMBL)
RAD50_HUMANProteinQ92878 (Uniprot-TrEMBL)
RAF1GeneProduct5894 (Entrez Gene)
RAP1AGeneProduct5906 (Entrez Gene)
RAP1BGeneProduct5908 (Entrez Gene)
RAPGEF1GeneProduct2889 (Entrez Gene)
RASA1GeneProduct5921 (Entrez Gene)
RB_HUMANProteinP06400 (Uniprot-TrEMBL)
RHEB_HUMANProteinQ15382 (Uniprot-TrEMBL)
RICTORProtein253260 (Entrez Gene)
RPTOR_HUMANProteinQ8N122 (Uniprot-TrEMBL)
SMAD2_HUMANProteinQ15796 (Uniprot-TrEMBL)Tumor supressor
SMAD3_HUMANProteinP84022 (Uniprot-TrEMBL)
SMARCA4GeneProduct6597 (Entrez Gene)
SMARCC1GeneProduct6599 (Entrez Gene)
SMARCC2GeneProduct6601 (Entrez Gene)
SMARCD1GeneProduct6602 (Entrez Gene)
SMARCD2GeneProduct6603 (Entrez Gene)
SMARCD3GeneProduct6604 (Entrez Gene)
SOS1GeneProduct6654 (Entrez Gene)Son of sevenless homolog 1 (Drosophila) (predicted)
SP1Protein6667 (Entrez Gene)DNA licensing factor for AR. Frequently occupies regions in enhancers with DNA recognition elements close to AR ARE
SPINK1GeneProduct6690 (Entrez Gene)
  • From Entrez Gene: The protein encoded by this gene is a trypsin inhibitor, which is secreted from pancreatic acinar cells into pancreatic juice. It is thought to function in the prevention of trypsin-catalyzed premature activation of zymogens within the pancreas and the pancreatic duct. Mutations in this gene are associated with hereditary pancreatitis and tropical calcific pancreatitis
  • Association with Prostate Cancer - Chinnaiyan Lab Cancer Cell Paper - ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers (∼10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers.
SPINK1ProteinD6RIU5 (Uniprot-TrEMBL)
SPRY1GeneProduct10252 (Entrez Gene)
SPRY2GeneProduct10253 (Entrez Gene)
STAT1_HUMANProteinP42224 (Uniprot-TrEMBL)
STAT3GeneProduct6774 (Entrez Gene)
SWI/SNFComplex
Steroid-19-HydroxylaseGeneProductENSG00000120054 (Ensembl)
TMPRSS2GeneProduct7113 (HGNC)
TRANSLATION
TSC1_HUMANProteinQ92574 (Uniprot-TrEMBL)
TSC2_HUMANProteinP49815 (Uniprot-TrEMBL)
TestosteroneMetabolite58-22-0 (CAS)
dehydroepiandrosteroneMetabolite53-43-0 (CAS)
p13KProtein
p14Protein
p15Protein
p21Protein
p27Protein
p38GeneProductENSG00000112062 (Ensembl)

Annotated Interactions

<cite>No annotated interactions</cite>