Document Detail

Down-regulation of Cdc6, a cell cycle regulatory gene, in prostate cancer.
MedLine Citation:
PMID:  12006585     Owner:  NLM     Status:  MEDLINE    
CDC6 plays a critical role in regulation of the onset of DNA replication in eukaryotic cells. We have found that Cdc6 expression is down-regulated in prostate cancer as detected by semiquantitative reverse transcriptase-PCR of prostate cell lines and laser-captured microdissected prostate tissues. This result was substantiated by immunohistochemical analysis of paraffin-embedded tissue sections and immunoblot analysis of benign (BPH-1) and adenocarcinomatous prostatic cells. Furthermore, a 100-fold reduction in the transcription efficiency of the Cdc6 promoter-luciferase construct was noted in the metastatic PC3 cells compared with that in BPH-1 cells. Concentration of the E2F and Oct1 transcription factors that have putative binding sites in the Cdc6 promoter was substantially low in PC3 cells compared with BPH cells. Mutagenesis of the two E2F binding sites on the Cdc6 promoter resulted in increased promoter activity in PC3 cells owing to elimination of the negative regulation by pRb.E2F complex but not to the level of that obtained in BPH cells. We conclude that an altered interaction of transcription factors may be responsible for the down-regulation of Cdc6 transcription in PC3 cells. Our study suggests a potential use of the lack of CDC6 expression as an index of prostate cancer development.
Liza D Robles; Andra R Frost; Monica Davila; Alan D Hutson; William E Grizzle; Ratna Chakrabarti
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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.     Date:  2002-05-02
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  277     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-07-08     Completed Date:  2002-08-12     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  25431-8     Citation Subset:  IM    
Department of Molecular Biology and Microbiology, University of Central Florida, Orlando 32826-2362, USA.
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MeSH Terms
Adenocarcinoma / genetics*,  pathology
Base Sequence
Binding Sites
Cell Cycle Proteins / genetics*
DNA Primers
DNA-Binding Proteins*
E2F Transcription Factors
Nuclear Proteins / genetics*
Promoter Regions, Genetic
Prostatic Neoplasms / genetics*,  pathology
RNA, Messenger / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors / metabolism
Transcription, Genetic
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/CDC6 protein, human; 0/Cell Cycle Proteins; 0/DNA Primers; 0/DNA-Binding Proteins; 0/E2F Transcription Factors; 0/Nuclear Proteins; 0/RNA, Messenger; 0/Transcription Factors

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