Document Detail


DNMT1 silencing affects locus specific DNA methylation and increases prostate cancer derived PC3 cell invasiveness.
MedLine Citation:
PMID:  19539327     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: DNMT1 maintains genomic DNA methylation at 5'-CpG-3' residues in somatic cells. Recent findings revealed that DNMT1 depletion causes distinct phenotypic changes in colon and gastric cancer cell lines, suggesting that the extent to which DNMT1 influences the expression of its target genes is cell-type specific. We determined the impact of DNMT1 depletion in prostate cancer derived cells on their gene expression profiles and cellular phenotype. MATERIALS AND METHODS: Small interfering RNA was used to silence DNMT1 expression in prostate cancer derived PC3 cells (ATCC). The resulting cell line was validated by reverse transcriptase-polymerase chain reaction and Western blotting. Proliferation, migration and invasion assays were done in engineered cells to asses the effect of DNMT1 silencing on cellular phenotype. DNA microarrays were done to monitor changes in gene expression. RESULTS: Our data showed that DNMT1 loss dramatically decreased cell proliferation but significantly increased cell migratory and invasive potential. Additionally, in the limited set of genes whose expression and DNA methylation status were determined DNMT1 loss was associated with increased CDKN3 and claudin-3 expression, and also culminated in specific demethylation of Rb1 and RAR-beta promoters. CONCLUSIONS: These results show that the genetic and phenotypic consequences of silencing DNMT1 in PC3 cells are markedly different from those in colon and gastric cancers, indicating that DNMT1 preferentially targets certain gene promoters. Our findings also suggest that decreasing DNMT1 levels or activity can potentially enhance prostate cancer cell invasiveness.
Authors:
Ahmed Yaqinuddin; Sohail A Qureshi; Romena Qazi; Salman Farooq; Farhat Abbas
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Publication Detail:
Type:  Journal Article     Date:  2009-06-18
Journal Detail:
Title:  The Journal of urology     Volume:  182     ISSN:  1527-3792     ISO Abbreviation:  J. Urol.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-14     Completed Date:  2009-08-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376374     Medline TA:  J Urol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  756-61     Citation Subset:  AIM; IM    
Affiliation:
Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
DNA (Cytosine-5-)-Methyltransferase / genetics*
DNA Methylation*
Gene Silencing*
Humans
Male
Neoplasm Invasiveness
Prostatic Neoplasms / genetics*,  pathology*
Chemical
Reg. No./Substance:
EC 2.1.1.37/DNA (Cytosine-5-)-Methyltransferase; EC 2.1.1.37/DNA (cytosine-5-)-methyltransferase 1

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


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