A role for GATA transcription factors in the androgen regulation of the prostate-specific antigen gene enhancer
A role for GATA transcription factors in the androgen regulation of the prostate-specific antigen gene enhancer
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DOI：
10.1016/s0303-7207(00)00300-2
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发表时间：
2000-09-25
影响因子：
4.1
通讯作者：
Roos, BA
中科院分区：
文献类型：
--
作者：
Perez-Stable, CM;de las Pozas, A;Roos, BA
含有与SV 40 T抗原连接的胎儿球蛋白启动子的转基因小鼠系G gamma/T-15意外地导致雄激素非依赖性前列腺癌。鉴于加塔-1转录因子在胎儿珠蛋白基因启动子活性中的关键作用，我们研究了特定的加塔家族成员是否在前列腺中表达以及它们是否可以调节前列腺特异性基因。我们发现，加塔-2和-3是人和小鼠前列腺中表达的主要加塔家族成员，并且加塔mRNA水平不受雄激素调节。我们确定了六个加塔网站侧翼雄激素反应元件位于前列腺特异性抗原（PSA）基因的远上游增强子。这些加塔位点是加塔因子的靶标，并且对于LNCaP（PSA和雄激素受体表达的人前列腺癌细胞系）中转染的PSA增强子/启动子质粒的最佳雄激素诱导是必需的。我们的研究结果表明，前列腺加塔-2和-3参与雄激素调节PSA基因。(C)2000爱思唯尔科学爱尔兰有限公司保留所有权利。
The transgenic mouse line G gamma/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. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.