The human papillomavirus type 18 E6 oncoprotein induces Vascular Endothelial Growth Factor 121 (VEGF121) transcription from the promoter through a p53-independent mechanism

Altered angiogenic response is associated with high-grade cervical dysplasia and with invasive squamous carcinoma of the cervix. Vascular Endothelial Growth Factor (VEGF) is one of the most potent inducers of angiogenesis and is up-regulated in carcinoma of the cervix. Infection by high-risk human papillomavirus and persistent expression of viral oncogene E6 are etiologically linked to the development of cervical cancer. E6 is able to immortalize cells and induce malignant transformation by inactivating p53. In cervical cancer, regulation of VEGF expression is poorly described. Thus, we investigated whether E6 oncoprotein could regulate VEGF expression in HPV18-positive cervical cancer-derived HeLa cells harboring a wild-type p53. The alternative splicing of vegf mRNA renders three major isoforms of 121, 165 and 189 amino-acids in humans. We have designed isoform specific real time QRT-PCR assays to quantitate vegf transcripts and VEGF121 was the predominant isoform. Silencing HPV18 E6 mRNA with specific siRNA reduced VEGF121 expression by at least 50% whereas silencing of p53 did not alter its expression. Treatment with cycloheximide did not inhibit E6-induced VEGF121 expression. Collectively, these results suggest that HPV18 E6 oncoprotein contributes to tumor angiogenesis by inducing VEGF transcription from the promoter in a p53-independent manner

The Antidiabetic Drug Ciglitazone Induces High Grade Bladder Cancer Cells Apoptosis through the Up-Regulation of TRAIL

International audienceBACKGROUND: Ciglitazone belongs to the thiazolidinediones class of antidiabetic drug family and is a high-affinity ligand for the Peroxisome Proliferator-Activated Receptor γ (PPARγ). Apart from its antidiabetic activity, this molecule shows antineoplastic effectiveness in numerous cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: Using RT4 (derived from a well differentiated grade I papillary tumor) and T24 (derived from an undifferentiated grade III carcinoma) bladder cancer cells, we investigated the potential of ciglitazone to induce apoptotic cell death and characterized the molecular mechanisms involved. In RT4 cells, the drug induced G2/M cell cycle arrest characterized by an overexpression of p53, p21(waf1/CIP1) and p27(Kip1) in concomitance with a decrease of cyclin B1. On the contrary, in T24 cells, it triggered apoptosis via extrinsic and intrinsic pathways. Cell cycle arrest and induction of apoptosis occurred at high concentrations through PPARγ activation-independent pathways. We show that in vivo treatment of nude mice by ciglitazone inhibits high grade bladder cancer xenograft development. We identified a novel mechanism by which ciglitazone kills cancer cells. Ciglitazone up-regulated soluble and membrane-bound TRAIL and let TRAIL-resistant T24 cells to respond to TRAIL through caspase activation, death receptor signalling pathway and Bid cleavage. We provided evidence that TRAIL-induced apoptosis is partially driven by ciglitazone-mediated down-regulation of c-FLIP and survivin protein levels through a proteasome-dependent degradation mechanism. CONCLUSIONS/SIGNIFICANCE: Therefore, ciglitazone could be clinically relevant as chemopreventive or therapeutic agent for the treatment of TRAIL-refractory high grade urothelial cancers

Latherin: A Surfactant Protein of Horse Sweat and Saliva

Horses are unusual in producing protein-rich sweat for thermoregulation, a major component of which is latherin, a highly surface-active, non-glycosylated protein. The amino acid sequence of latherin, determined from cDNA analysis, is highly conserved across four geographically dispersed equid species (horse, zebra, onager, ass), and is similar to a family of proteins only found previously in the oral cavity and associated tissues of mammals. Latherin produces a significant reduction in water surface tension at low concentrations (≤1 mg ml−1), and therefore probably acts as a wetting agent to facilitate evaporative cooling through a waterproofed pelt. Neutron reflection experiments indicate that this detergent-like activity is associated with the formation of a dense protein layer, about 10 Å thick, at the air-water interface. However, biophysical characterization (circular dichroism, differential scanning calorimetry) in solution shows that latherin behaves like a typical globular protein, although with unusual intrinsic fluorescence characteristics, suggesting that significant conformational change or unfolding of the protein is required for assembly of the air-water interfacial layer. RT-PCR screening revealed latherin transcripts in horse skin and salivary gland but in no other tissues. Recombinant latherin produced in bacteria was also found to be the target of IgE antibody from horse-allergic subjects. Equids therefore may have adapted an oral/salivary mucosal protein for two purposes peculiar to their lifestyle, namely their need for rapid and efficient heat dissipation and their specialisation for masticating and processing large quantities of dry food material

Les variables biologiques au service de la gestion des écosystèmes aquatiques

Aquatic system management involves various actors : the contracting authority (local communities, industrialists...) that is responsible for the decision, the State services (DDE, DDAF, DRIRE...) that are responsible for the regulation, and the water agencies, that are responsible for financial support within the framework of the "water laws". The 16 December 1964 law concerned the fight against pollution and the protection of water uses and led to the development, in 1971, of a national inventory of pollution and then to a policy with quality as its goal. The 3 January 1992 law which positions on again, and completes, the law of 1964, is based on the definition of the goals for environment quality, and no longer on the goals for water quality, and on quantitative goals. In the management of aquatic systems, the biological approach which is a complement of the chemical analysis will have to be looked at again. Moreover, managers should be given simple management tools, a challenge that must be picked up by the scientists. The improvement of the management tools is based on the continuous reinforcement of the basic biological knowledge. / La gestion des systèmes aquatiques fait intervenir divers acteurs, la décision incombant au maître d'ouvrage (collectivités territoriales, industriels, ...), la régle- mentation aux services de l'Etat (DDE, DDAF, DRIRE, ...), l'incitation financière aux Agences de l'eau dans un cadre défini par des "lois sur l'eau". La loi du 16 décembre 1964 s'intéressait à la lutte contre la pollution et à la protection des usages de l'eau et a conduit en 1971 au développement d'un inventaire national de la pollution et à une politique des objectifs de qualité. La loi du 3 janvier 1992 repose sur la définition d'objectifs de qualité du milieu, et non plus seulement de l'eau, et d'objectifs de quantité. Dans la gestion des systèmes aquatiques, l'approche biologique, qui se place en complément de l'analyse chimique devra être repositionnée et des outils de gestion simples devront être fournis aux décideurs, défi que les scientifiques auront à relever. De plus, l'amélioration des outils de gestion repose sur le renforcement continu des connaissances biologiques de base

L'affinité de deux protozoaires épibiontes pour les deux espèces jumelles de planaires d'eau douce Polycelis nigra et Polycelis tenuis

L'étude porte sur l'association de commensalisme liant les deux Planaires jumelles Polycelis nigra et P. tenuis à deux Protozoaires Ciliés épibiontes de la famille des Urceolariidae. Urceolaria mitra est nettement majoritaire sur Polycelis tenuis, et Trichodina steini exclusive sur Polycelis nigra. Des expériences de choix attestent la préférence indiscutable des épibiontes pour leur espèce affine de Planaire

Les réseaux d'observation et de surveillance

The structured observation networks aims to maintain and develop the knowledge basis on aquatic environments in order to understand their status and follow their evolution. The concept of a network is associated not only with the double notion of permanence and of spatial cover but also with the concept of efficiency and the warning function. Networks must be designed as an answer to the problematics and according to a reference system which allows a given situation, and an eventual gap compared with this reference system, to be assessed at a given time. The monitoring networks of the quality of the river (such as National network of basin, complementary basin networks) are the oldest. They are dedicated to the study of basic physico-chemical parameters, metallic and organic micropollutants, biological parameters, invertebrate fauna and the other biological groups. There is no national network type device for the monitoring of water stretches. On coastal areas, the French organization IFREMER manages the National Monitoring Network of the quality of the marine environment (RENO), the Phytoplancton Monitoring Network (REPHY) and the Microbiological Monitoring Network (REMI). The improvement in the operation of these networks is based on the selection of the most suitable methods for the problem encountered, the standardization of protocols, and the valorization of the obtained data. / Les réseaux d'observation structurés permettent d'entretenir et de développer le fonds de connaissance sur les milieux aquatiques, pour en connaître l'état et pour en suivre l'évolution. Au concept de réseau sont associés la double notion de permanence et de couverture spatiale mais également le concept d'efficacité et la fonction d'alerte. Les réseaux doivent être conçus en réponse à une problématique et selon un référentiel permettant d'apprécier à un instant donné, une situation donnée et un écart éventuel par rapport à ce référentiel. Les réseaux d'observation de la qualité des cours d'eau (Réseau national de bassin, réseaux complémentaires de bassin) sont les plus anciens. Ils ont pour vocation l'étude des paramètres physico-chimiques de base, des micropolluants métalliques et organiques, des paramètres biologiques, de la faune invertébrée et des autres groupes biologiques. Aucun dispositif national de type réseau n'existe pour l'observation des plans d'eau. Au niveau du littoral marin, l'IFREMER gère le Réseau national d'observation de la qualité du milieu marin (RENO), le Réseau d'observation du phytoplancton (REPHY) et le Réseau d'observation microbiologique (REMI). L'amélioration du fonction- nement de ces réseaux repose sur une sélection des méthodes les plus adaptées au problème rencontré, la normalisation des protocoles, la valorisation des données recueillies

Le traitement et le rejet d'effluents municipaux en fonction des elements et des milieux recepteurs

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