Systematic name M11619
Brief description Genes down-regulated in MDA-MB-231 cells (breast cancer) after knockdown of PRKCA and ETS1 [GeneID=5578;2113] by RNAi.
Full description or abstract PKCalpha 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 PKCalpha expression (siPalpha) 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 siPalpha interferes with both Ets1 protein synthesis and stability. The effect of siPalpha 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 PKCalpha-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 PKCalpha/Ets1 interaction, we compared the biological responses of MDA-MB-231 cells to PKCalpha- and Ets1-specific siRNAs (siE1). While only siPalpha 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 siPalpha and siE1. The data suggest that Ets1 serves as an effector for PKCalpha to fulfil certain functions in cancer cells.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 15531915   Authors: Vetter M,Blumenthal SG,Lindemann RK,Manns J,Wesselborg S,Thomssen C,Dittmer J
Exact source Table 1: log2 (fold induction) < 0
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(show 2 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
Source platform HUMAN_GENE_SYMBOL
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Version history 3.0: First introduced

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