A role for GATA transcription factors in the androgen regulation of the prostate-specific antigen gene enhancer.
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.
Perez-Stable
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Geriatric Research, Education, and Clinical Center and Research Service, Veterans Affairs Medical Center, Miami, FL 33125, USA. cpsma@msn.com
Pozas
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D000818:Animals; D001943:Breast Neoplasms; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005260:Female; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D050993:GATA6 Transcription Factor; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011471:Prostatic Neoplasms; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014566:Urogenital System / Q000254:growth & development / Q000378:metabolism; D016335:Zinc Fingers / Q000235:genetics
D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; C494712:Gata2 protein, mouse; C494748:Gata3 protein, mouse; C494760:Gata6 protein, mouse; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D017430:Prostate-Specific Antigen