The presence of androgen receptor elements regulates ZEB1 expression in the absence of androgen receptor

Steven M. Mooney, Princy Parsana, James R. Hernandez, Xin Liu, James E. Verdone, Gonzalo Torga, Calvin A. Harberg, Kenneth J. Pienta

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Zinc finger E-box binding homeobox1 (ZEB1) is a transcription factor that playsa central role in the epithelial to mesenchymal transition (EMT) of cancer cell lines. Studies on its regulation have mostly focused on the negative 3'UTR binding of miR200c. Interestingly, it has been previously reported that androgen receptor (AR) regulates ZEB1 expression in breast and prostate cancers. In order to validate this, various ZEB1 promoter deletions were cloned into a luciferase reporter system to elucidate the contribution of two putative androgen response elements (AREs). The in vivo contribution of AR was also assessed in cell lines after R1881 treatment using qPCR with prostate specific antigen (PSA) as the positive control. We discovered that AR upregulates the levels of expression of ZEB1 10-fold on a luciferase promoter that only contains the distal ARE. However, when the proximal ARE is included, no additional activation is apparent with AR or its hormone independent variant, AR-V7. Furthermore, we demonstrate here that a promoter construct containing both AREs activates transcriptionof ZEB1 even in the AR-null cell lines DU145and PC3. Incubation ofthe AR-positive cell line, LNCaP with R1881, failedto substantially increase the expression levelsof ZEB1.Despite the presenceof AREs in the promoter region, it appears that ZEB1 expression can beinduced even without AR. In addition, the region around the distal ARE is a potent repressor in AR-null cell lines.

Original languageEnglish (US)
Pages (from-to)115-123
Number of pages9
JournalJournal of cellular biochemistry
Issue number1
StatePublished - Jan 1 2015


  • Androgen Receptor (AR)
  • Epithelial to mesenchymal transition (EMT)
  • Luciferase assays
  • OVOL1
  • OVOL2
  • Prostate cancer
  • ZEB1/TCF8

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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