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Papers In Press, published online ahead of print April 12, 2004
Endocrinologie Moléculaire de la Reproduction, UMR CNRS 6026, RENNES, Cedex 35042
Corresponding Author: Gilles.Flouriot{at}univ-rennes1.fr
The activity of the transactivation functions (AF-1 and AF-2) of the estrogen receptor alpha (ER
J. Biol. Chem, 10.1074/jbc.M402148200
Submitted on February 26, 2004
Revised on April 9, 2004
Accepted on April 12, 2004
The relative contribution exerted by AF-1 and AF-2 transactivation functions in estrogen receptor alpha (ER
) transcriptional activity depends upon the differentiation stage of the cell
) 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 ER AFs in two different cases: i) 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 towards ER activity varies in a cell differentiation stage dependent manner. Specifically, whilst AF-1 is the dominant AF involved in ER transcriptional activity in differentiated cells, the more a cell is dedifferentiated and the more this cell mediates ER 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 ER in strictly AF-2 permissive cells restores an AF-1 sensitive cell context. These results, together with data obtained in different ER positive cell lines tested strongly suggest that the transcriptional activity of ER relies on its AF-1 in most of estrogen target cell types.
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