This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zha, S. Articles by Isaacs, W. B. Search for Related Content PubMed PubMed Citation Articles by Zha, S. Articles by Isaacs, W. B.

---

Signaling and Regulation

A Nonclassic CCAAT Enhancer Element Binding Protein Binding Site Contributes to -Methylacyl-CoA Racemase Expression in Prostate Cancer

¹ Brady Urological Institute and ² Johns Hopkins Oncology Center, Johns Hopkins Medical Institutions, Baltimore, Maryland

Requests for reprints: William B. Isaacs, Department of Urology, Johns Hopkins Hospital, Marburg 115, 600 North Wolfe Street, Baltimore, MD 21287. Phone: 410-955-2518; Fax: 410-955-0833. E-mail: wisaacs{at}jhmi.edu

-Methylacyl-CoA racemase (AMACR), an enzyme involved in branched-chain fatty acid ß-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 ß 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 gene expression.

Key Words: -methylacyl-CoA racemase • CCAAT/enhancer binding protein • prostate cancer • methylation