15-PGJ2, but not thiazolidinediones, inhibits cell growth, induces apoptosis, and causes downregulation of Stat3 in human oral SCCa cells

Activation of peroxisome proliferator-activated receptor gamma (PPARγ) has been linked to induction of differentiation, cell growth inhibition and apoptosis in several types of human cancer. However, the possible effects of PPARγ agonists on human oral squamous cell carcinoma have not yet been reported. In this study, treatment with 15-deoxy-Δ12,14-PGJ2 (15-PGJ2), a natural PPARγ ligand, induced a significant reduction of oral squamous cell carcinoma cell growth, which was mainly attributed to upregulation of apoptosis. Interestingly, rosiglitazone and ciglitazone, two members of the thiazolidinedione family of PPARγ activators, did not exert a growth inhibitory effect. Given the critical role that the oncogene signal transducer and activator of transcription 3 (Stat3) plays in head and neck carcinogenesis, its potential regulation by PPARγ ligands was also examined. Treatment of oral squamous cell carcinoma cells with 15-PGJ2 induced an initial reduction and eventual elimination of both phosphorylated and unphosphorylated Stat3 protein levels. In contrast, other PPARγ did not induce similar effects. Our results provide the first evidence of significant antineoplastic effects of 15-PGJ2 on human oral squamous cell carcinoma cells, which may be related to downmodulation of Stat3 and are at least partly mediated through PPARγ-independent events

Multiple Roles for the Non-Coding RNA SRA in Regulation of Adipogenesis and Insulin Sensitivity

Peroxisome proliferator-activated receptor-γ (PPARγ) is a master transcriptional regulator of adipogenesis. Hence, the identification of PPARγ coactivators should help reveal mechanisms controlling gene expression in adipose tissue development and physiology. We show that the non-coding RNA, Steroid receptor RNA Activator (SRA), associates with PPARγ and coactivates PPARγ-dependent reporter gene expression. Overexpression of SRA in ST2 mesenchymal precursor cells promotes their differentiation into adipocytes. Conversely, knockdown of endogenous SRA inhibits 3T3-L1 preadipocyte differentiation. Microarray analysis reveals hundreds of SRA-responsive genes in adipocytes, including genes involved in the cell cycle, and insulin and TNFα signaling pathways. Some functions of SRA may involve mechanisms other than coactivation of PPARγ. SRA in adipocytes increases both glucose uptake and phosphorylation of Akt and FOXO1 in response to insulin. SRA promotes S-phase entry during mitotic clonal expansion, decreases expression of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1, and increases phosphorylation of Cdk1/Cdc2. SRA also inhibits the expression of adipocyte-related inflammatory genes and TNFα-induced phosphorylation of c-Jun NH2-terminal kinase. In conclusion, SRA enhances adipogenesis and adipocyte function through multiple pathways

SS18 Together with Animal-Specific Factors Defines Human BAF-Type SWI/SNF Complexes

Contains fulltext : 94049.pdf (publisher's version ) (Open Access

Qualifier le manque d'eau et gouverner les conflits d'usage : le cas des débits d'objectif d'étiage (DOE) en Adour-Garonne

International audienceThis paper studies the processes involved in the mutual definition of devices that objectify and govern water scarcity in the Adour-Garonne district. It first discusses the manner the problem of water scarcity has been historically and socially shaped. It analyses the mechanisms that have legitimized and institutionalized a specific socio-technical infrastructure that reduces water to its flow. It then explores how such socio-technical infrastructure frames the negotiations concerning water at a local scale. It shows how hydrologic, hydraulic and agricultural knowledge are actively involved in naturalizing water uses; while it also produces new problems which regulation involves renewing the control and consistency of different spatialities and temporalitiesCet article étudie les processus par lesquels se redéfinissent mutuellement des dispositifs de qualification et de gestion du manque d'eau dans le bassin Adour-Garonne. Il discute d'abord les processus par lesquels la pénurie d'eau s'est historiquement imposée en décrivant l'institutionnalisation et la légitimation progressive d'une infrastructure sociotechnique réduisant la qualification et la gestion de l'eau à son débit. Il analyse ensuite comment cette infrastructure cadre, à l'échelle locale, les négociations. Il montre comment la mobilisation de savoirs hydrologiques, hydrauliques et agronomiques contribue à naturaliser certains usages de l'eau, tout en produisant aussi de nouveaux problèmes qui sont régulés en renouvelant la maîtrise et la mise en cohérence de différentes temporalités et spatialités