STANDARD_NAME	VETTER_TARGETS_OF_PRKCA_AND_ETS1_UP
SYSTEMATIC_NAME	M14495
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/VETTER_TARGETS_OF_PRKCA_AND_ETS1_UP
NAMESPACE	HUMAN_GENE_SYMBOL
DESCRIPTION_BRIEF	Genes up-regulated in MDA-MB-231 cells (breast cancer) after knockdown of PRKCA and ETS1 [GeneID=5578;2113] by RNAi.
DESCRIPTION_FULL	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.
PMID	15531915
GEOID	
AUTHORS	Vetter M,Blumenthal SG,Lindemann RK,Manns J,Wesselborg S,Thomssen C,Dittmer J
CONTRIBUTOR	Leona Saunders
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 1: log2 (fold induction) > 0
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	ARL7,BCL11A,DIAPH1,DKFZp566C0424,FN1,HS2ST1,INSIG1,NICE-4,PEG10,PML,RHOBTB3,RUNX1,SCAMP1,SEC23IP,TGFB2,TRPC1
GENE_SYMBOLS	ARL4C,BCL11A,DIAPH1,SZRD1,FN1,HS2ST1,INSIG1,UBAP2L,PEG10,PML,RHOBTB3,RUNX1,SCAMP1,SEC23IP,TGFB2,TRPC1
FOUNDER_NAMES	
