Document Detail

Promoter methylation correlates with reduced Smad4 expression in advanced prostate cancer.
MedLine Citation:
PMID:  18213629     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Transforming growth factor-beta (TGF-beta) is a potent growth inhibitor in a wide range of cell types. A transducer of TGF-beta signaling known as Mothers against decapentaplegic homologue 4 (Smad4) is a known tumor suppressor found on chromosome 18q21.1 and is typically inactivated by deletion or mutation in pancreatic and colorectal cancers. The purpose of the article is to investigate Smad4 expression, gene copy number and methylation status in advanced cases of prostate cancer.
METHODS: We have employed Methylation Specific PCR (MSP) to identify methylation sites within the Smad4 promoter and combined this with quantitative real-time PCR to look for correlates between methylation status and Smad4 expression and to examine androgen receptor (AR) expression. Bacterial artificial chromosome-comparative genomic hybridization (BAC-CGH) has been used to look for genomic amplifications and deletions which may also contribute to expression changes.
RESULTS: We fail to find evidence of genomic deletions or amplifications affecting the Smad4 locus on chromosome 18 but show a correlation between promoter methylation and the loss of Smad4 expression in the same material. We confirm that the AR locus on the X chromosome is amplified in 30% of the advanced clinical samples and that this correlates with increased transcript levels as previously reported by other groups.
CONCLUSION: This indicates that epigenetic changes affect the expression of the Smad4 protein in prostate cancer and points to methylation of the promoter as a novel marker of and contributor to the disease warranting further study.
Alan A Aitchison; Abhi Veerakumarasivam; Maria Vias; Rajeev Kumar; Freddie C Hamdy; David E Neal; Ian G Mills
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Prostate     Volume:  68     ISSN:  0270-4137     ISO Abbreviation:  Prostate     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-03-24     Completed Date:  2008-06-03     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  8101368     Medline TA:  Prostate     Country:  United States    
Other Details:
Languages:  eng     Pagination:  661-74     Citation Subset:  IM    
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MeSH Terms
Adenocarcinoma / genetics*,  metabolism,  pathology
Cell Line, Tumor
Chromosomes, Artificial, Bacterial
Chromosomes, Human, X
DNA Methylation*
DNA, Neoplasm / analysis
Neoplasm Recurrence, Local
Nucleic Acid Hybridization
Promoter Regions, Genetic*
Prostatic Neoplasms / genetics*,  metabolism,  pathology
Smad4 Protein / genetics*,  metabolism
Tumor Markers, Biological / genetics,  metabolism
Grant Support
G0500966//Medical Research Council; //Cancer Research UK
Reg. No./Substance:
0/DNA, Neoplasm; 0/Oligonucleotides; 0/SMAD4 protein, human; 0/Smad4 Protein; 0/Tumor Markers, Biological

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

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