Transcription of the caveolin-1 gene is differentially regulated in lung type I epithelial and endothelial cell lines - A role for ETS proteins in epithelial cell expression

Transcription of the caveolin-1 gene is differentially regulated in lung type I epithelial and endothelial cell lines - A role for ETS proteins in epithelial cell expression
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DOI:
10.1074/jbc.m402236200
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发表时间:
2004-07-16
影响因子:
4.8
通讯作者:
Williams, MC
Williams, MC
中科院分区:
生物学2区
文献类型:
--
作者:
Kathuria, H;Cao, YX;Williams, MC

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在肺中,小窝蛋白-1在I型肺泡上皮细胞和内皮细胞中表达,假设其调节分子信号传导活性和肿瘤发生的进展。在发育过程中,小窝蛋白-1 α在胎儿肺内皮细胞中表达,但在上皮细胞中不表达;在成人肺中,两种细胞类型都表达小窝蛋白-1 α。为了验证小窝蛋白-1转录在I型细胞和内皮细胞中受到差异调节的假设,我们表征了肺细胞系中小鼠小窝蛋白-1基因的近端启动子,以确定控制其细胞特异性表达的因素。我们发现,小窝蛋白-1的表达是由一个Ets顺式元件在肺上皮细胞系,但不是肺内皮细胞系,和三个ETS家族成员,ETS-1,PEA 3,和ERM,识别和结合的Ets网站在上皮细胞系。基于这些发现,我们已经确定了Ets顺式元件作为一个区域,占差异转录调节小窝蛋白-1在肺上皮细胞和内皮细胞。
In the lung, caveolin-1 is expressed in both type I alveolar epithelial and endothelial cells where it is hypothesized to modulate molecular signaling activities and progression of tumorigenesis. Developmentally, caveolin-1alpha is expressed in fetal lung endothelial, but not epithelial, cells; in adult lung, both cell types express caveolin-1alpha. To test the hypothesis that caveolin-1 transcription is differentially regulated in type I and endothelial cells, we characterized the proximal promoter of the mouse caveolin-1 gene in lung cell lines to identify factors that control its cell-specific expression. We show that caveolin-1 expression is regulated by an Ets cis-element in a lung epithelial cell line, but not a lung endothelial cell line, and that three ETS family members, ETS-1, PEA3, and ERM, recognize and bind the Ets site in the epithelial cell line. Based on these findings, we have identified the Ets cis-element as a region that accounts for differential transcriptional regulation of caveolin-1 in lung epithelial and endothelial cells.