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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Locus-wide chromatin remodeling and enhanced androgen receptor-mediated transcription in recurrent prostate tumor cells
Molecular and Cellular Biology, Volume 26, No. 19, Year 2006
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Description
Prostate cancers (PCas) become resistant to hormone withdrawal through increased androgen receptor (AR) signaling. Here we show increased AR-mediated transcription efficiency in PCa cells that have acquired the ability to grow in low concentrations of androgen. Compared to androgen-dependent PCa cells, these cells showed increased activity of transiently transfected reporters and increased mRNA synthesis relative to levels of AR occupancy of the prostate-specific antigen (PSA) gene. The locus also displayed up to 10-fold-higher levels of histone H3-K9/K14 acetylation and H3-K4 methylation across the entire body of the gene. Although similar increased mRNA expression and locus-wide histone acetylation were also observed at another kallikrein locus (KLK2), at a third AR target locus (TMPRSS2) increased gene expression and locus-wide histone acetylation were not seen in the absence of ligand. Androgen-independent PCa cells have thus evolved three distinctive alterations in AR-mediated transcription. First, increased RNA polymerase initiation and processivity contributed to increased gene expression. Second, AR signaling was more sensitive to ligand. Third, locus-wide chromatin remodeling conducive to the increased gene expression in the absence of ligand was apparent and depended on sustained AR activity. Therefore, increased AR ligand sensitivity as well as locus-specific chromatin alterations contribute to basal gene expression of a subpopulation of specific AR target genes in androgen-independent PCa cells. These features contribute to the androgen-independent phenotype of these cells. Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Shen, Howard C.
United States, Los Angeles
Keck School of Medicine of Usc
Stanczyk, Frank Z.
United States, Los Angeles
Keck School of Medicine of Usc
Jones, Peter A.
United States, Los Angeles
Keck School of Medicine of Usc
Coetzee, Gerhard A.
United States, Los Angeles
Keck School of Medicine of Usc
Statistics
Citations: 66
Authors: 4
Affiliations: 1
Identifiers
Doi:
10.1128/MCB.00581-06
ISSN:
02707306
Research Areas
Cancer
Genetics And Genomics