Prolactin expression is induced in Jurkat T-cells by beta-catenin LEF-1, AP-1 and cAMP.
Prolactin expression is induced in Jurkat T-cells by beta-catenin LEF-1, AP-1 and cAMP.
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Jurkat T 细胞中催乳素表达由 β-连环蛋白 LEF-1、AP-1 和 cAMP 诱导。
DOI：
10.1016/j.bbrc.2007.01.023
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发表时间：
2007
影响因子：
3.1
通讯作者：
Reem,GH
中科院分区：
文献类型：
--
作者：
Andria,ML;Reem,GH
人类的催乳素（PRL）是在垂体和垂体外部位产生的。近端启动子需要Pit-1转录因子控制垂体PRL表达，而位于垂体起始位点上游5.8kb的远端（上游）启动子调节垂体外PRL合成。我们以前曾报道，cAMP调节PRL的转录在Jurkat淋巴细胞部分通过cAMP反应元件。在这里，我们证明了对应于LEF-1和AP-1转录因子结合位点的额外的PRL调控元件对于PRL表达似乎是重要的，因为当这些位点缺失或突变时，EMSA和报告基因表达的因子结合减少。有趣的是，组成型活性形式的β-连环蛋白的过表达增加Jurkat细胞的PRL表达。这种作用通过依赖和非依赖两种途径发生。我们的研究确定了PRL远端启动子作为β-catenin的靶点，并揭示了调节垂体外PRL表达的新途径。
Prolactin (PRL) in humans is produced in the pituitary as well as in extra-pituitary sites. A proximal promoter that requires the Pit-1 transcription factor controls pituitary PRL expression, whereas a distal (upstream) promoter located at 5.8kb upstream of the pituitary start site regulates extra-pituitary PRL synthesis. We have previously reported that cAMP regulates PRL transcription in Jurkat lymphocytes in part through a cAMP responsive element. Here we demonstrate that additional PRL regulatory elements corresponding to LEF-l and AP-1 transcription factor binding sites appear important for PRL expression, since factor binding by EMSA and reporter gene expression are reduced when these sites are deleted or mutated. Interestingly, over-expression of a constitutively active form of β-catenin increases PRL expression of Jurkat cells. This effect occurs through both LEF-dependent and -independent pathways. Our studies identify the distal PRL promoter as a target for β-catenin, and reveal novel pathways regulating extra-pituitary PRL expression.