Prostate cancer (PCa) is one of the major public health problems in Western countries. Recently, the TMPRSS2:ERG gene fusion, which results in the aberrant expression of the transcription factor ERG, ...has been shown to be the most common gene rearrangement in PCa. Previous studies have determined the contributions of this fusion in PCa disease initiation and/or progression in vitro and in vivo. In this study on TMPRSS2:ERG regulation in PCa, we used an androgen receptor and TMPRSS2:ERG fusion double-negative PCa cell model: PC3c. In three cell clones with different TMPRSS2:ERG expression levels, ectopic expression of the fusion resulted in significant induction of cell migration and invasion in a dose-dependent manner. In agreement with this phenotype, high-throughput microarray analysis revealed that a set of genes, functionally associated with cell motility and invasiveness, were deregulated in a dose-dependent manner in TMPRSS2:ERG-expressing cells. Importantly, we identified increased MMP9 (Metalloproteinase 9) and PLXNA2 (Plexin A2) expression in TMPRSS2:ERG-positive PCa samples, and their expression levels were significantly correlated with ERG expression in a PCa cohort. In line with these findings, there was evidence that TMPRSS2:ERG directly and positively regulates MMP9 and PLXNA2 expression in PC3c cells. Moreover, PLXNA2 upregulation contributed to TMPRSS2:ERG-mediated enhancements of PC3c cell migration and invasion. Furthermore, and importantly, PLXNA2 expression was upregulated in metastatic PCa tumors compared with localized primary PCa tumors. This study provides novel insights into the role of the TMPRSS2:ERG fusion in PCa metastasis.
Objective: The aim of this study is to determine the effect of coenzyme Q (Q) on ob/ob mice treated or not with thiazolidinedione (TZD). Design and measurements: Ob/ob mice were treated with Q, ...Rosiglitazone or a combination of both molecules for 13 days; physical and metabolic parameters as well as oral glucose tolerance test were assessed. mRNA expression of genes of energy dissipation and storage were measured by real-time PCR. Results: Q treatment improved some metabolic parameters in ob/ob mice. Surprisingly, cotreatment with Rosiglitazone and Q improved metabolic parameters and prevented TZD increase in body weight and adiposity, mainly by increasing lipid oxidation in adipose tissue, reducing lipid synthesis and balancing adipokine gene expression. Conclusions: Our finding suggests that Rosiglitazone and coenzyme Q bitherapy could prevent the body weight gain associated with adipogenesis and could improve the clinical use of these compounds.
Résumé Le projet PROMOCART (2007–2010) a été retenu suite à l’appel 2006 ANR-TecSan. Il a été conduit par le laboratoire « Biologie et ingénierie du cartilage » (Lyon) en partenariat avec les ...laboratoires « Matrice extracellulaire et pathologie » (Caen), l’institut de biologie de Lille, la société Symatèse biomatériaux (Chaponost) et le laboratoire des substituts cutanés des hospices civils de Lyon. Le cartilage est un tissu au potentiel de cicatrisation spontané très limité. La transplantation de chondrocytes autologues (TCA) est une technique mondialement utilisée pour le traitement de lésions limitées de cartilage articulaire. Cependant, cette approche implique une amplification des chondrocytes sur plastique, ce qui entraîne leur dédifférenciation. Un premier objectif de PROMOCART était de déterminer si la bone morphogenetic protein (BMP)-2 est capable de favoriser le maintien ou la restauration du phénotype des chondrocytes humains. Dans le but d’étendre la TCA à des lésions cartilagineuses plus importantes comme celles des arthroses débutantes, nous avons développé un procédé de reconstruction de cartilage humain dans des éponges de collagène en présence de BMP-2 et dans des conditions hypoxiques. Nous avons contrôlé la qualité du phénotype cellulaire par l’utilisation de nouveaux marqueurs du cartilage.
Vitamin A derivatives plays a crucial role in embryonic development, as demonstrated by the teratogenic effect of either an excess or a deficiency in vitamin A. Retinoid effects extend however beyond ...embryonic development, and tissue homeostasis, lipid metabolism, cellular differentiation and proliferation are in part controlled through the retinoid signaling pathway. Retinoids are also therapeutically effective in the treatment of skin diseases (acne, psoriasis and photoaging) and of some cancers. Most of these effects are the consequences of retinoic acid receptors activation, which triggers transcriptional events leading either to transcriptional activation or repression of retinoid-controlled genes. Synthetic molecules are able to mimic part of the biological effects of the natural retinoic acid receptors, all-trans retinoic acid. Therefore, retinoic acid receptors are considered as highly valuable therapeutic targets and limiting unwanted secondary effects due to retinoid treatment requires a molecular knowledge of retinoic acid receptors biology. In this review, we will examine experimental evidence which provide a molecular basis for the pleiotropic effects of retinoids, and emphasize the crucial roles of coregulators of retinoic acid receptors, providing a conceptual framework to identify novel therapeutic targets.
Project PROMOCART (2007–2010) was adopted following the call 2006 ANR-TecSan. It was led by the laboratory of Biology and Engineering of Cartilage (Lyon), and carried out in partnership with the ...laboratory of Extracellular Matrix and Pathology (Caen), Lille Institute of Biology, Symatèse Biomatériaux company (Chaponost) and laboratory of Skin Substitutes (Lyon Hospital). Cartilage presents poor intrinsic healing capacity. Autologous chondrocyte implantation (ACI) is a worldwide used technique applied to focal defects of articular cartilage. However, it implies a step of cell amplification on plastic, which results in the loss of chondrocyte differentiation. The first objective of PROMOCART was to determine if bone morphogenetic protein (BMP)-2 could maintain or restore the differentiated phenotype of human chondrocytes. With the view of applying ACI to developing osteoarthritic lesions, we developed a new method of human cartilage reconstruction by using collagen sponges, BMP-2 and hypoxic culture conditions. We controlled the quality of the cellular phenotype by using new cartilage markers.
Le projet PROMOCART (2007–2010) a été retenu suite à l’appel 2006 ANR-TecSan. Il a été conduit par le laboratoire « Biologie et ingénierie du cartilage » (Lyon) en partenariat avec les laboratoires « Matrice extracellulaire et pathologie » (Caen), l’institut de biologie de Lille, la société Symatèse biomatériaux (Chaponost) et le laboratoire des substituts cutanés des hospices civils de Lyon. Le cartilage est un tissu au potentiel de cicatrisation spontané très limité. La transplantation de chondrocytes autologues (TCA) est une technique mondialement utilisée pour le traitement de lésions limitées de cartilage articulaire. Cependant, cette approche implique une amplification des chondrocytes sur plastique, ce qui entraîne leur dédifférenciation. Un premier objectif de PROMOCART était de déterminer si la bone morphogenetic protein (BMP)-2 est capable de favoriser le maintien ou la restauration du phénotype des chondrocytes humains. Dans le but d’étendre la TCA à des lésions cartilagineuses plus importantes comme celles des arthroses débutantes, nous avons développé un procédé de reconstruction de cartilage humain dans des éponges de collagène en présence de BMP-2 et dans des conditions hypoxiques. Nous avons contrôlé la qualité du phénotype cellulaire par l’utilisation de nouveaux marqueurs du cartilage.
Project PROMOCART (2007–2010) was adopted following the call 2006 ANR-TecSan. It was led by the laboratory of Biology and Engineering of Cartilage (Lyon), and carried out in partnership with the ...laboratory of Extracellular Matrix and Pathology (Caen), Lille Institute of Biology, Symatèse Biomatériaux company (Chaponost) and laboratory of Skin Substitutes (Lyon Hospital). Cartilage presents poor intrinsic healing capacity. Autologous chondrocyte implantation (ACI) is a worldwide used technique applied to focal defects of articular cartilage. However, it implies a step of cell amplification on plastic, which results in the loss of chondrocyte differentiation. The first objective of PROMOCART was to determine if bone morphogenetic protein (BMP)-2 could maintain or restore the differentiated phenotype of human chondrocytes. With the view of applying ACI to developing osteoarthritic lesions, we developed a new method of human cartilage reconstruction by using collagen sponges, BMP-2 and hypoxic culture conditions. We controlled the quality of the cellular phenotype by using new cartilage markers.
Le projet PROMOCART (2007–2010) a été retenu suite à l’appel 2006 ANR-TecSan. Il a été conduit par le laboratoire « Biologie et ingénierie du cartilage » (Lyon) en partenariat avec les laboratoires « Matrice extracellulaire et pathologie » (Caen), l’institut de biologie de Lille, la société Symatèse biomatériaux (Chaponost) et le laboratoire des substituts cutanés des hospices civils de Lyon. Le cartilage est un tissu au potentiel de cicatrisation spontané très limité. La transplantation de chondrocytes autologues (TCA) est une technique mondialement utilisée pour le traitement de lésions limitées de cartilage articulaire. Cependant, cette approche implique une amplification des chondrocytes sur plastique, ce qui entraîne leur dédifférenciation. Un premier objectif de PROMOCART était de déterminer si la bone morphogenetic protein (BMP)-2 est capable de favoriser le maintien ou la restauration du phénotype des chondrocytes humains. Dans le but d’étendre la TCA à des lésions cartilagineuses plus importantes comme celles des arthroses débutantes, nous avons développé un procédé de reconstruction de cartilage humain dans des éponges de collagène en présence de BMP-2 et dans des conditions hypoxiques. Nous avons contrôlé la qualité du phénotype cellulaire par l’utilisation de nouveaux marqueurs du cartilage.
Retinoic acid receptors (RARs) are the molecular relays of retinoid action on transcription, cellular differentiation and apoptosis. Transcriptional activation of retinoid-regulated promoters ...requires the dismissal of corepressors and the recruitment of coactivators to promoter-bound RAR. RARs recruit in vitro a plethora of coactivators whose actual contribution to retinoid-induced transcription is poorly characterized in vivo. Embryonal carcinoma P19 cells, which are highly sensitive to retinoids, were depleted from archetypical coactivators by RNAi. SRC1-deficient P19 cells showed severely compromised retinoid-induced responses, in agreement with the supposed role of SRC1 as a RAR coactivator. Unexpectedly, Med1/TRAP220/DRIP205-depleted cells exhibited an exacerbated response to retinoids, both in terms transcriptional responses and of cellular differentiation. Med1 depletion affected TFIIH and cdk9 detection at the prototypical retinoid-regulated RARβ2 promoter, and favored a higher RNA polymerase II detection in transcribed regions of the RARβ2 gene. Furthermore, the nature of the ligand impacted strongly on the ability of RARs to interact with a given coactivator and to activate transcription in intact cells. Thus RAR accomplishes transcriptional activation as a function of the ligand structure, by recruiting regulatory complexes which control distinct molecular events at retinoid-regulated promoters.
RREB-1 is a transcriptional repressor of HLA-G Flajollet, Sébastien; Poras, Isabelle; Carosella, Edgardo D ...
The Journal of immunology (1950),
2009-Dec-01, Letnik:
183, Številka:
11
Journal Article
Recenzirano
Odprti dostop
The nonclassical HLA-G is a molecule specifically involved in immune tolerance with highly restricted tissue distribution in healthy conditions. Yet it is overexpressed in numerous tumors and in ...allografts with better acceptance. Major mechanisms involved in regulation of HLA-G transcription are still poorly described. Thus, to characterize these mechanisms we have developed a specific proteomic approach to identify proteins that bind differentially to the HLA-G gene promoter by promoter pull-down assay followed by spectrometry mass analysis. Among specific binding factors, we focused on RREB-1, a ras-responsive element binding protein 1. We demonstrated that RREB-1 represses HLA-G transcriptional activity and binds three ras response elements within the HLA-G promoter. RREB-1 protein, specifically in HLA-G-negative cells, interacts with subunits of CtBP complex implicated in chromatin remodeling. This demonstration is the first of a repressor factor of HLA-G transcriptional activity taking part in HLA-G repression by epigenetic mechanisms.
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