NKX-3.1 interacts with prostate-derived Ets factor and regulates the activity of the PSA promoter

Cancer Res. 2002 Jan 15;62(2):338-40.

Abstract

The NKX-3.1 homeobox gene maps to human chromosome 8p21, a region that undergoes frequent loss of heterozygosity in prostate tumors. Loss of Nkx-3.1 function in mice leads to epithelial overgrowth. To further elucidate the molecular basis of NKX-3.1 function, a genetic screen for proteins that interact with NKX-3.1 was performed. Prostate-derived Ets factor (PDEF) was identified as a potential partner of NKX-3.1. Coimmunoprecipitation analyses demonstrated that NKX-3.1 and PDEF are physically associated in prostate epithelial cells. Cotransfection analyses demonstrated that NKX-3.1 can abolish the transcriptional activation function of PDEF on the prostate-specific antigen (PSA) promoter. These data identify PSA as a target gene for NKX-3.1 and provide new insights into the function of this candidate tumor suppressor.

Publication types

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

MeSH terms

  • Epithelial Cells / metabolism
  • Epithelial Cells / physiology
  • Gene Expression Regulation
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Male
  • Precipitin Tests
  • Promoter Regions, Genetic / genetics
  • Prostate / metabolism*
  • Prostate / physiology
  • Prostate-Specific Antigen / genetics*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Proto-Oncogene Proteins c-ets
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Homeodomain Proteins
  • NKX3-1 protein, human
  • Proto-Oncogene Proteins c-ets
  • SPDEF protein, human
  • Transcription Factors
  • Prostate-Specific Antigen