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

Oncogene volume 24, pages 4946–4955 (2005)Cite this article

Abstract

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 (PKC). PKCδ is a particular isoenzyme of the novel PKC subfamily that plays a role in growth control, differentiation and apoptosis. The aim of the present study was to investigate the impact of PKCδ on the regulation of the transcriptional activity of the human ERα. By using 12-O-tetradecanoylphorbol-13-acetate (TPA), Bryostatin1 and Rottlerin, we show that active PKCδ is a proproliferative factor in estrogen-dependent breast cancer cells. Furthermore, activation of PKCδ by TPA resulted in activation and nuclear translocation of ERα and in an increase of ER-dependent reporter gene expression. Transfection and expression of the regulatory domain RDδ of PKCδ, which is inhibitory to PKCδ, inhibited the TPA-induced ERα activation and translocation. ERα was not phosphorylated by PKCδ; however, glycogen synthase kinase-3 (GSK3) was identified as a substrate of PKCδ. The expression of RDδ resulted in a decrease of TPA-induced GSK3 phosphorylation and translocation into the nucleus. We suggest that GSK3 plays a role in the PKCδ-related nuclear translocation of ERα.

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Abbreviations

DAG:

diacylglycerol

ER:

estrogen receptor

ERE:

estrogen response element

PKC:

protein kinase C

PMSF:

phenylmethylsulfonyl fluoride

PS:

phosphatidylserine

RDδ:

regulatory domain of PKCδ

TPA:

12-O-tetradecanoylphorbol-13-acetate

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Acknowledgements

We thank G Rincke for valuable technical assistance. B De Servi was recipient of a visiting scientist fellowship from the German Cancer Research Centre.

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  1. Deutsches Krebsforschungszentrum, Hormones and Signal Transduction, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany

    Barbara De Servi, Alexander Hermani, Senad Medunjanin & Doris Mayer

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  1. Barbara De Servi
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  2. Alexander Hermani
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  3. Senad Medunjanin
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Correspondence to Doris Mayer.

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De Servi, B., Hermani, A., Medunjanin, S. et al. Impact of PKCδ on estrogen receptor localization and activity in breast cancer cells. Oncogene 24, 4946–4955 (2005). https://doi.org/10.1038/sj.onc.1208676

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