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Ets1 is an effector of protein kinase Cα in cancer cells

Oncogene volume 24, pages 650–661 (2005)Cite this article

A Corrigendum to this article was published on 16 June 2005

Abstract

PKCα and Ets1 are both associated with breast cancer progression. Our previous studies suggested that these proteins are likely to functionally interact with one another. Here, we show that attenuation of endogenous PKCα expression (siPα) by RNA interference leads to reduced Ets1 protein expression in a variety of cancer cells. Pulse-chase experiments and treatment with proteasome inhibitor MG-132 revealed that siPα interferes with both Ets1 protein synthesis and stability. The effect of siPα on Ets1 expression could be partially prevented by KN-93, suggesting that calcium/calmodulin-dependent kinase II (CaMKII), a modulator of Ets1 activity, may play a role in PKCα-dependent Ets1 regulation. In contrast, Ets1-regulating kinases ERK1/2 were not found to be involved in this process. To assess the importance of the PKCα/Ets1 interaction, we compared the biological responses of MDA-MB-231 cells to PKCα- and Ets1-specific siRNAs (siE1). While only siPα induced changes in cellular morphology and anchorage-independent growth, both siRNAs similarly affected cellular responses to the antitumor drug mithramycin A and to UV light. Microarray analyses further showed that the expression of a certain set of genes was equally affected by siPα and siE1. The data suggest that Ets1 serves as an effector for PKCα to fulfil certain functions in cancer cells.

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Acknowledgements

We like to thank Pearl Campbell and Katayoun Sheikheleslamy for performing the microarray analyses. This work was supported by BMBF-Grant NBL3 FKZ5/14.

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Author notes

  1. Ralph K Lindemann

    Present address: Gene Regulation Laboratory, Cancer Immunology Division, The Peter MacCallum Cancer Institute, Smorgon Family Building, St Andrews Place, East Melbourne, 3002, Victoria, Australia

  2. Martina Vetter and Sibylle G Blumenthal: These authors contributed equally to this work.

Authors and Affiliations

  1. Universität Halle-Wittenberg, Universitätsklinik und Poliklinik für Gynäkologie, Ernst-Grube-Str. 40, 06097, Halle (Saale), Germany

    Martina Vetter, Christoph Thomssen & Jürgen Dittmer

  2. Abteilung Innere Medizin I, Med. Klinik, Eberhard-Karls-Universität, Otfried-Müller-Str. 10, 72076, Tübingen, Germany

    Sibylle G Blumenthal, Ralph K Lindemann, Joachim Manns & Sebastian Wesselborg

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Correspondence to Jürgen Dittmer.

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Vetter, M., Blumenthal, S., Lindemann, R. et al. Ets1 is an effector of protein kinase Cα in cancer cells. Oncogene 24, 650–661 (2005). https://doi.org/10.1038/sj.onc.1208234

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