Impact of PKCdelta on estrogen receptor localization and activity in breast cancer cells.

Regulation of estrogen receptor (ER) function in breast cancer cells is a complex process involving different signalling mechanisms. One signal transduction component that appears to influence ER signalling is protein kinase C is a particular isoenzyme of the novel subfamily that plays a role in growth control, differentiation and apoptosis. The aim of the present study was to investigate the impact of duanyu1531delta on the regulation of the transcriptional activity of the human ERalpha. By using 12-O-tetradecanoylphorbol-13-acetate (TPA), Bryostatin1 and Rottlerin, we show that active duanyu1531delta is a proproliferative factor in estrogen-dependent breast cancer cells. Furthermore, activation of duanyu1531delta by TPA resulted in activation and nuclear translocation of ERalpha and in an increase of ER-dependent reporter gene expression. Transfection and expression of the regulatory domain RDdelta of which is inhibitory to duanyu1531delta, inhibited the TPA-induced ERalpha activation and translocation. ERalpha was not phosphorylated by however, glycogen synthase kinase-3 (GSK3) was identified as a substrate of The expression of RDdelta resulted in a decrease of TPA-induced GSK3 phosphorylation and translocation into the nucleus. We suggest that GSK3 plays a role in the nuclear translocation of ERalpha.

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