在一种乳腺上皮细胞系中，白血病抑制因子（LIF）会损害信号转导及转录激活因子5（STAT5）的转录活性。

STAT5 transcriptional activity is impaired by LIF in a mammary epithelial cell line.

作者信息

Granillo Agustina Rodriguez, Boffi Juan Carlos, Barañao Lino, Kordon Edith, Pecci Adali, Guberman Alejandra

机构信息

Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pab. II, Piso 2, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.

出版信息

Biochem Biophys Res Commun. 2007 May 11;356(3):727-32. doi: 10.1016/j.bbrc.2007.03.040. Epub 2007 Mar 16.

DOI:10.1016/j.bbrc.2007.03.040

PMID:17382296

Abstract

Gene regulation mediated by STAT factors has been implicated in cellular functions with relevance to a variety of processes. Particularly, STAT5 and STAT3 play a crucial role in mammary epithelium displaying reciprocal activation kinetics during pregnancy, lactation and involution. Here, we show that LIF treatment of mammary epithelial HC11 cells reduces the phosphorylation levels and transcriptional activity of p-STAT5 in correlation with STAT3 phosphorylation. We have also found that STAT5 activity is negatively modulated by this cytokine, both on a gene whose expression is induced, as well as on a promoter repressed by STAT5. Besides, our results show that lactogenic hormones increase LIF effect on gene induction without modifying STAT3 phosphorylation state. Our findings strongly suggest that there is crosstalk between STAT5 and STAT3 pathways that could modulate their ability to regulate gene expression.

摘要

由信号转导和转录激活因子（STAT）介导的基因调控与多种细胞功能相关，涉及各种生理过程。特别是，STAT5和STAT3在乳腺上皮细胞中起着至关重要的作用，在怀孕、哺乳和退化过程中表现出相互激活的动力学。在这里，我们表明，白血病抑制因子（LIF）处理乳腺上皮HC11细胞会降低p-STAT5的磷酸化水平和转录活性，这与STAT3磷酸化相关。我们还发现，这种细胞因子对STAT5活性具有负调控作用，无论是在其表达被诱导的基因上，还是在被STAT5抑制的启动子上。此外，我们的结果表明，催乳激素增加了LIF对基因诱导的作用，而不改变STAT3的磷酸化状态。我们的研究结果强烈表明，STAT5和STAT3信号通路之间存在相互作用，这可能会调节它们调控基因表达的能力。