Ets1 is an effector of protein kinase Cα in cancer cells

• Published in: Oncogene Vol. 24; no. 4; pp. 650 - 661
• Main Authors: Vetter, Martina, Blumenthal, Sibylle G, Lindemann, Ralph K, Manns, Joachim, Wesselborg, Sebastian, Thomssen, Christoph, Dittmer, Jürgen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.01.2005; Nature Publishing; Nature Publishing Group
• Subjects: Apoptosis; Biological and medical sciences; Cell Biology; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Fundamental and applied biological sciences. Psychology; Gynecology. Andrology. Obstetrics; Human Genetics; Internal Medicine; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Molecular and cellular biology; Oncology; original-paper; Tumors; Ets transcription factors; breast cancer; RNA interference; protein kinase C; Mammary gland diseases; Gene silencing; Protein kinase C; Enzyme; Protein kinase; Transferases; Breast cancer; Malignant tumor; Carcinogenesis
• ISSN: 0950-9232; 1476-5594; 1476-5594
• DOI: 10.1038/sj.onc.1208234

PKC α 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 PKC α expression (siP α ) 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 siP α interferes with both Ets1 protein synthesis and stability. The effect of siP α 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 PKC α -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 PKC α /Ets1 interaction, we compared the biological responses of MDA-MB-231 cells to PKC α - and Ets1-specific siRNAs (siE1). While only siP α 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 siP α and siE1. The data suggest that Ets1 serves as an effector for PKC α to fulfil certain functions in cancer cells.