Document Detail


A molecular genetic model of human bladder cancer pathogenesis.
MedLine Citation:
PMID:  8893868     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
An understanding of the biological significance of the multiple genetic alterations identified in clinical bladder cancers to the stepwise pathogenesis of the disease is evolving. Alterations in p53 and pRb, products of the chromosomes 17p13 TP53 and 13q14 RB tumor suppressor genes, occur in approximately 50% and approximately 33% of bladder cancers respectively, and are associated with later stage, higher grade disease. p53 and pRb alterations are also known to occur in early stage bladder carcinoma in situ where they are thought to represent a poor prognosis for tumor progression. Allelic loss of genes on 9p21 occurs in approximately 50% of bladder cancers, but whether the only critical gene in this region is the CDKN2/p16 cyclin/CDK inhibitor is at present uncertain. Amplification and/or overexpression of the oncogenes epidermal growth factor receptor and erbB2 are associated with later stage disease. Finally, recent findings generated using in vitro transformation systems with human uroepithelial cells provide strong evidence that loss of genes on 3p, which occurs in approximately 20% of bladder cancers, and/or gain of genes on 20q play an important role in blocking HUC cellular senescence. This latter phenotype should represent a critical step in oncogenesis, as cells that do not senesce can survive to accumulate the multiple genetic alterations associated with invasive and metastatic bladder cancers. Further understanding of the biochemical mechanisms underlying these genetic changes will provide the additional information needed to design better strategies for bladder cancer intervention and treatment.
Authors:
C A Reznikoff; C D Belair; T R Yeager; E Savelieva; R H Blelloch; J A Puthenveettil; S Cuthill
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  Seminars in oncology     Volume:  23     ISSN:  0093-7754     ISO Abbreviation:  Semin. Oncol.     Publication Date:  1996 Oct 
Date Detail:
Created Date:  1996-11-27     Completed Date:  1996-11-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0420432     Medline TA:  Semin Oncol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  571-84     Citation Subset:  IM    
Affiliation:
University of Wisconsin Medical School, Department of Human Oncology, Madison, USA.
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MeSH Terms
Descriptor/Qualifier:
Chromosome Aberrations
Genes, p53
Humans
Models, Genetic
Urinary Bladder Neoplasms / etiology,  genetics*
Grant Support
ID/Acronym/Agency:
R01-CA29525-15/CA/NCI NIH HHS; R01-CA67158-1/CA/NCI NIH HHS

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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