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

Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, Maryland 21250, USA.
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.
Mesh Terms:
Epithelial Cells, Gene Expression Regulation, Homeodomain Proteins, Humans, Male, Precipitin Tests, Promoter Regions, Genetic, Prostate, Prostate-Specific Antigen, Prostatic Neoplasms, Proto-Oncogene Proteins c-ets, Transcription Factors, Transcriptional Activation, Transfection, Tumor Cells, Cultured
Cancer Res. Jan. 15, 2002; 62(2);338-40 [PUBMED:11809674]
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