KEGG   DISEASE: H00024Help
Entry
H00024                      Disease                                

Name
Prostate cancer
Description
Prostate cancer constitutes a major health problem in Western countries. It is the most frequently diagnosed cancer among men and the second leading cause of male cancer deaths. The identification of key molecular alterations in prostate-cancer cells implicates carcinogen defenses (GSTP1), growth-factor-signaling pathways (NKX3.1, PTEN, and p27), and androgens (AR) as critical determinants of the phenotype of prostate-cancer cells. Glutathione S-transferases (GSTP1) are detoxifying enzymes. Cells of prostatic intraepithelial neoplasia, devoid of GSTP1, undergo genomic damage mediated by carcinogens. NKX3.1, PTEN, and p27 regulate the growth and survival of prostate cells in the normal prostate. Inadequate levels of PTEN and NKX3.1 lead to a reduction in p27 levels and to increased proliferation and decreased apoptosis. Androgen receptor (AR) is a transcription factor that is normally activated by its androgen ligand. During androgen withdrawal therapy, the AR signal transduction pathway also could be activated by amplification of the AR gene, by AR gene mutations, or by altered activity of AR coactivators. Through these mechanisms, tumor cells lead to the emergence of androgen-independent prostate cancer.
Category
Cancer
BRITE hierarchy
Pathway
Prostate cancer
Transcriptional misregulation in cancers
MicroRNAs in cancer
Gene
AR (amplification, mutation) [HSA:367] [KO:K08557]
CDKN1B (allelic loss) [HSA:1027] [KO:K06624]
NKX3.1 (allelic loss) (decreased expression) [HSA:4824] [KO:K09348]
PTEN (allelic loss) [HSA:5728] [KO:K01110]
GSTP1 (hypermethylation) [HSA:2950] [KO:K00799]
TMPRSS2-ERG (translocation) [HSA:7113 2078] [KO:K09633 K09435]
TMPRSS2-ETV1 (translocation) [HSA:7113 2115] [KO:K09633 K09431]
TMPRSS2-ETV4 (translocation) [HSA:7113 2118] [KO:K09633 K15592]
TMPRSS2-ETV5 (translocaiton) [HSA:7113 2119] [KO:K09633 K15593]
SLC45A3-ETV1 (translocation) [HSA:85414 2115] [KO:K15379 K09431]
SLC45A3-ELK4 (translocation) [HSA:85414 2005] [KO:K15379 K04376]
DDX5-ETV4 (translocaiton) [HSA:1655 2118] [KO:K12823 K15592]
Carcinogen
Cadmium and cadmium compounds [CPD:C01413]
Chimney sweeping
Marker
PSA [HSA:354]
GSTP1 (hypermethylation) [HSA:2950]
AMACR [HSA:23600]
Telomerase [HSA:7015]
PCA3 (prostate-specific non-coding RNA)
TB-15 (thymosin beta15)
Drug
Leuprolide [DR:D00989]
Goserelin [DG:DG00731]
Triptorelin [DG:DG00732]
Flutamide [DR:D00586]
Comment
ICD-O: 8140/3, Tumor type: Adenocarcinoma (acinar)
ICD-O: 8148/2, Tumor type: Prostatic intraepithelial neoplasia, glade III (PIN III)
Other DBs
ICD-10: 
Reference
PMID:12878745 (gene, tumor type)
  Authors
Nelson WG, De Marzo AM, Isaacs WB.
  Title
Prostate cancer.
  Journal
N Engl J Med 349:366-81 (2003)
Reference
PMID:17384581 (gene, tumor type)
  Authors
De Marzo AM, Platz EA, Sutcliffe S, Xu J, Gronberg H, Drake CG, Nakai Y, Isaacs WB, Nelson WG.
  Title
Inflammation in prostate carcinogenesis.
  Journal
Nat Rev Cancer 7:256-69 (2007)
Reference
PMID:11018010 (tumor type)
  Authors
Abate-Shen C, Shen MM.
  Title
Molecular genetics of prostate cancer.
  Journal
Genes Dev 14:2410-34 (2000)
Reference
PMID:15149739 (gene)
  Authors
Porkka KP, Visakorpi T.
  Title
Molecular mechanisms of prostate cancer.
  Journal
Eur Urol 45:683-91 (2004)
Reference
PMID:19406209 (gene)
  Authors
Brenner JC, Chinnaiyan AM
  Title
Translocations in epithelial cancers.
  Journal
Biochim Biophys Acta 1796:201-15 (2009)
Reference
PMID:15660110 (carcinogen)
  Authors
Luch A.
  Title
Nature and nurture - lessons from chemical carcinogenesis.
  Journal
Nat Rev Cancer 5:113-25 (2005)
Reference
PMID:9498904 (carcinogen)
  Authors
Boffetta P, Jourenkova N, Gustavsson P.
  Title
Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons.
  Journal
Cancer Causes Control 8:444-72 (1997)
Reference
PMID:17303324 (marker)
  Authors
Reynolds MA, Kastury K, Groskopf J, Schalken JA, Rittenhouse H.
  Title
Molecular markers for prostate cancer.
  Journal
Cancer Lett 249:5-13 (2007)
Reference
PMID:17092277 (marker)
  Authors
Downes MR, Byrne JC, Pennington SR, Dunn MJ, Fitzpatrick JM, Watson RW.
  Title
Urinary markers for prostate cancer.
  Journal
BJU Int 99:263-8 (2007)
Reference
PMID:16945550 (marker)
  Authors
van der Poel HG.
  Title
Molecular markers in the diagnosis of prostate cancer.
  Journal
Crit Rev Oncol Hematol 61:104-39 (2007)
Reference
(drug)
  Authors
McPhee SJ, Papadakis MA, Tierney LM (ed).
  Title
Current Medical Diagnosis & Treatment 2007, Forty-Sixth Edition
  Journal
The McGraw-Hill Companies, Inc. (2007)

» Japanese version

DBGET integrated database retrieval system