The relative contribution exerted by AF-1 and AF-2 transactivation functions in estrogen receptor α transcriptional activity depends upon the differentiation stage of the cell
The relative contribution exerted by AF-1 and AF-2 transactivation functions in estrogen receptor α transcriptional activity depends upon the differentiation stage of the cell
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DOI：
10.1074/jbc.m402148200
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发表时间：
2004-06-18
影响因子：
4.8
通讯作者：
Flouriot, G
中科院分区：
文献类型：
--
作者：
Mérot, Y;Métivier, R;Flouriot, G
雌激素受体α(ERpha)的激活功能(激活功能(AF)-1和AF-2)的活性是细胞特异性的。这项研究旨在破译目前尚不清楚的这种细胞分化敏感性的机制，特别关注细胞分化对这些过程的具体影响。因此，我们在两种不同的情况下比较评估了细胞对ERphaAFS的许可程度：(I)一系列起源于共同组织但具有不同分化表型的细胞株；(Ii)在培养中经历分化过程的细胞株。这些实验表明，AF-1和AF-2对ERpha活性的贡献分别随细胞分化阶段的不同而不同。具体地说，尽管AF-1是分化细胞中参与ERpha转录活动的主要AF，但细胞去分化越多，该细胞就越多地通过AF-2介导ERpha信号。例如，AF-2是细胞中唯一实现上皮-间充质转化的活跃的AF。此外，在严格的AF-2允许的细胞中，功能性ERpha的稳定表达恢复了AF-1敏感的细胞环境。这些结果，加上在不同的ERα阳性细胞株中测试的数据强烈表明，在大多数雌激素靶细胞类型中，ERα的转录活性依赖于它的AF-1。
The activity of the transactivation functions (activation function (AF)-1 and AF-2) of the estrogen receptor alpha (ERalpha) is cell-specific. This study aimed to decipher the yet unclear mechanisms involved in this differential cell sensitivity, with particular attention to the specific influence that cell differentiation may have on these processes. Hence, we comparatively evaluated the permissiveness of cells to either ERalpha AFs in two different cases: (i) a series of cell lines originating from a common tissue, but with distinct differentiation phenotypes; and (ii) cell lines that undergo differentiation processes in culture. These experiments demonstrate that the respective contribution that AF-1 and AF-2 make toward ERalpha activity varies in a cell differentiation stage-dependent manner. Specifically, whereas AF-1 is the dominant AF involved in ERalpha transcriptional activity in differentiated cells, the more a cell is de-differentiated the more this cell mediates ERalpha signaling through AF-2. For instance, AF-2 is the only active AF in cells that have achieved their epithelial-mesenchymal transition. Moreover, the stable expression of a functional ERalpha in strictly AF-2 permissive cells restores an AF-1-sensitive cell context. These results, together with data obtained in different ERalpha-positive cell lines tested strongly suggest that the transcriptional activity of ERalpha relies on its AF-1 in most estrogen target cell types.