Document Detail


Evolution of the concept of androgen-sensitive bladder cancer.
MedLine Citation:
PMID:  23330817     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Abstract This reviews describes the concept of androgen-dependent growth of bladder cancer and the role of single-nucleotide polymorphisms (SNPs) located on chromosome 8q24 as a common carcinogenetic pathway for the development of concomitant prostate and bladder cancer. Recent genome-wide association studies have identified high-risk SNPs on chromosome 8q24 that have been linked with increased susceptibility for bladder and prostate cancer and alterations in the androgen receptor (AR) pathway. Muscle-invasive bladder cancers overexpress the AR, whereas in locally advanced or lymph-node positive stages loss of AR expression has been found. The prostate stem cell antigen (PSCA) gene possesses an androgen-responsive element (ARE) in its promoter region. Heterozymous and homozygous carriers of the SNP rs22940008 in the first exon of the PSCA gene are at increased risk for invasive bladder cancers. They exhibit significantly lower PSCA messenger RNA expression than patients with the wild-type genotype. Loss of the AR responsivity of the PSCA promoter may be a result of an altered affinity of the AR to the ARE mediated by the rs2294008 SNP or reduced expression of AR coactivators. Thereafter, induction of an androgen-independent mechanism, i.e. the insulin-like growth factor binding protein-2 signalling pathway - a key event in the development of hormone-independent prostate cancer - may increase tumour aggressiveness and metastatic potential of invasive bladder cancer cells. Loss of PSCA expression may represent an important step for androgen-independent growth, linked with the presence of the rs2294008 SNP. Determination of the AR status in cystectomy specimens offers new therapeutic approaches in locally advanced bladder cancer.
Authors:
Georgios Gakis; Arnulf Stenzl; Markus Renninger
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-21
Journal Detail:
Title:  Scandinavian journal of urology     Volume:  -     ISSN:  2168-1813     ISO Abbreviation:  Scand J Urol     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101587186     Medline TA:  Scand J Urol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Urology, Eberhard-Karls University , Tübingen , Germany.
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