A role for GATA transcription factors in the androgen regulation of the prostate-specific antigen gene enhancer

Mol Cell Endocrinol. 2000 Sep 25;167(1-2):43-53. doi: 10.1016/s0303-7207(00)00300-2.

Abstract

The transgenic mouse line Ggamma/T-15 containing the fetal globin promoter linked to SV40 T antigen unexpectedly results in androgen-independent prostate carcinomas. Given the key role of GATA-1 transcription factor in fetal globin gene promoter activity, we investigated whether specific GATA family members are expressed in the prostate and whether they can regulate prostate-specific genes. We found that GATA-2 and -3 are the predominant GATA family members expressed in human and mouse prostate and that GATA mRNA levels are not regulated by androgen. We identified six GATA sites flanking an androgen-response element located in the far-upstream enhancer of the prostate-specific antigen (PSA) gene. These GATA sites are targets for GATA factors and are essential for optimal androgen induction of transfected PSA enhancer/promoter plasmids in LNCaP, a PSA and androgen receptor expressing human prostate cancer cell line. Our results suggest that prostatic GATA-2 and -3 are involved in the androgen regulation of the PSA gene.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Breast Neoplasms
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Electrophoresis, Polyacrylamide Gel
  • Enhancer Elements, Genetic / genetics*
  • Female
  • GATA2 Transcription Factor
  • GATA3 Transcription Factor
  • GATA6 Transcription Factor
  • Gene Expression Regulation
  • Genes, Reporter
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Mutagenesis, Site-Directed
  • Promoter Regions, Genetic / genetics*
  • Prostate-Specific Antigen / genetics*
  • Prostatic Neoplasms
  • Protein Binding
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured
  • Urogenital System / growth & development
  • Urogenital System / metabolism
  • Zinc Fingers / genetics

Substances

  • DNA-Binding Proteins
  • GATA2 Transcription Factor
  • GATA2 protein, human
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • GATA6 Transcription Factor
  • GATA6 protein, human
  • Gata2 protein, mouse
  • Gata3 protein, mouse
  • Gata6 protein, mouse
  • RNA, Messenger
  • Trans-Activators
  • Transcription Factors
  • Prostate-Specific Antigen