STANDARD_NAME	CAFFAREL_RESPONSE_TO_THC_8HR_5_UP
SYSTEMATIC_NAME	M17987
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/CAFFAREL_RESPONSE_TO_THC_8HR_5_UP
NAMESPACE	HUMAN_GENE_SYMBOL
DESCRIPTION_BRIEF	Genes up-regulated in EVSA-T cells (breast cancer) treated with 5 micromolar THC (delta-9-tetrahydrocannabinol) [PubChem=6610319] for 8 h.
DESCRIPTION_FULL	It has been recently shown that cannabinoids, the active components of marijuana and their derivatives, inhibit cell cycle progression of human breast cancer cells. Here we studied the mechanism of Delta(9)-tetrahydrocannabinol (THC) antiproliferative action in these cells, and show that it involves the modulation of JunD, a member of the AP-1 transcription factor family. THC activates JunD both by upregulating gene expression and by translocating the protein to the nuclear compartment, and these events are accompanied by a decrease in cell proliferation. Of interest, neither JunD activation nor proliferation inhibition was observed in human non-tumour mammary epithelial cells exposed to THC. We confirmed the importance of JunD in THC action by RNA interference and genetic ablation. Thus, in both JunD-silenced human breast cancer cells and JunD knockout mice-derived immortalized fibroblasts, the antiproliferative effect exerted by THC was significantly diminished. Gene array and siRNA experiments support that the cyclin-dependent kinase inhibitor p27 and the tumour suppressor gene testin are candidate JunD targets in cannabinoid action. In addition, our data suggest that the stress-regulated protein p8 participates in THC antiproliferative action in a JunD-independent manner. In summary, this is the first report showing not only that cannabinoids regulate JunD but, more generally, that JunD activation reduces the proliferation of cancer cells, which points to a new target to inhibit breast cancer progression.
PMID	18454173
GEOID	GSE8502
AUTHORS	Caffarel MM,Moreno-Bueno G,Cerutti C,Palacios J,Guzman M,Mechta-Grigoriou F,Sanchez C
CONTRIBUTOR	Jessica Robertson
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 4S
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	AA446839,C20orf111,CDKN1B,CTSL,GARS,GOLGB1,ID2,IPO7,JTV1,JUND,SRRM2,STX5,TES,TncRNA,USP3,ZFP36L1
GENE_SYMBOLS	,OSER1,CDKN1B,CTSL,GARS1,GOLGB1,ID2,IPO7,AIMP2,JUND,SRRM2,STX5,TES,NEAT1,USP3,ZFP36L1
FOUNDER_NAMES