A nonclassic CCAAT enhancer element binding protein binding site contributes to α-methylacyl-CoA racemace expression in prostate cancer

Research output: Contribution to journalArticle

Abstract

α-Methylacyl-CoA racemase (AMACR), an enzyme involved in branched-chain fatty acid β-oxidation that is normally expressed at high levels in human liver, is specifically and consistently overexpressed at both mRNA and protein levels in human prostate cancer and potentially other cancer types. To characterize the mechanisms underlying transcriptional regulation of AMACR at the genetic and epigenetic levels, we performed a series of methylation and reporter assays in prostate cancer tissues and cell lines. The results ruled out altered methylation patterns as the cause of overexpression in prostate cancer cells. However, promoter deletion analysis identified an 8-bp nonclassic CCAAT enhancer element located ≃80 bp upstream of the transcriptional initiation site that is responsible for AMACR expression in both prostate cancer cell lines and cell lines of liver origin. Deletion or mutation of this element completely abolished AMACR promoter activity. Ectopic expression of CCAAT/enhancer binding protein β increased luciferase activity driven by a wild-type AMACR promoter sequence but not by the sequence in which the putative CCAAT/enhancer binding protein binding element had been mutated. These results implicate a nonclassic CCAAT enhancer element in the AMACR gene promoter as playing a critical role in the regulation of AMACR aene expression.

Original languageEnglish (US)
Pages (from-to)110-118
Number of pages9
JournalMolecular Cancer Research
Volume3
Issue number2
DOIs
StatePublished - Feb 2005

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CCAAT-Enhancer-Binding Proteins
Coenzyme A
Protein Binding
Prostatic Neoplasms
Binding Sites
Cell Line
Methylation
Racemases and Epimerases
Sequence Deletion
Liver
Luciferases
Epigenomics
Fatty Acids
Messenger RNA
Enzymes
Genes
Neoplasms
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

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title = "A nonclassic CCAAT enhancer element binding protein binding site contributes to α-methylacyl-CoA racemace expression in prostate cancer",
abstract = "α-Methylacyl-CoA racemase (AMACR), an enzyme involved in branched-chain fatty acid β-oxidation that is normally expressed at high levels in human liver, is specifically and consistently overexpressed at both mRNA and protein levels in human prostate cancer and potentially other cancer types. To characterize the mechanisms underlying transcriptional regulation of AMACR at the genetic and epigenetic levels, we performed a series of methylation and reporter assays in prostate cancer tissues and cell lines. The results ruled out altered methylation patterns as the cause of overexpression in prostate cancer cells. However, promoter deletion analysis identified an 8-bp nonclassic CCAAT enhancer element located ≃80 bp upstream of the transcriptional initiation site that is responsible for AMACR expression in both prostate cancer cell lines and cell lines of liver origin. Deletion or mutation of this element completely abolished AMACR promoter activity. Ectopic expression of CCAAT/enhancer binding protein β increased luciferase activity driven by a wild-type AMACR promoter sequence but not by the sequence in which the putative CCAAT/enhancer binding protein binding element had been mutated. These results implicate a nonclassic CCAAT enhancer element in the AMACR gene promoter as playing a critical role in the regulation of AMACR aene expression.",
author = "Shan Zha and Isaacs, {William B}",
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AB - α-Methylacyl-CoA racemase (AMACR), an enzyme involved in branched-chain fatty acid β-oxidation that is normally expressed at high levels in human liver, is specifically and consistently overexpressed at both mRNA and protein levels in human prostate cancer and potentially other cancer types. To characterize the mechanisms underlying transcriptional regulation of AMACR at the genetic and epigenetic levels, we performed a series of methylation and reporter assays in prostate cancer tissues and cell lines. The results ruled out altered methylation patterns as the cause of overexpression in prostate cancer cells. However, promoter deletion analysis identified an 8-bp nonclassic CCAAT enhancer element located ≃80 bp upstream of the transcriptional initiation site that is responsible for AMACR expression in both prostate cancer cell lines and cell lines of liver origin. Deletion or mutation of this element completely abolished AMACR promoter activity. Ectopic expression of CCAAT/enhancer binding protein β increased luciferase activity driven by a wild-type AMACR promoter sequence but not by the sequence in which the putative CCAAT/enhancer binding protein binding element had been mutated. These results implicate a nonclassic CCAAT enhancer element in the AMACR gene promoter as playing a critical role in the regulation of AMACR aene expression.

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