Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Increasingly, health risk assessment is addressing multiple pathway exposures to multiple contaminants. We reviewed aggregated exposure and cumulative risk approaches for contemporary and ubiquitous semivolatile organic compounds (SVOC). We identified 22 studies aggregating exposure pathways, and 31 cumulating risk. Exposure aggregation is based on the addition of pathway-specific doses, using kinetic modeling where it exists, and classic external dose equations otherwise. In most cases, exposure is dominated by a single route or source of exposure - mainly the oral pathway - via dietary or non-dietary exposure. Preferential routes and sources of exposure are influenced by SVOC physical-chemical properties such as vapor pressure. The cumulative risk approach for contaminants is based on dose addition. Simple sum of hazard quotient (Hazard Index: HI) is the most commonly used cumulative risk assessment approach, while Relative Potency Factor (RPF) appeared to the best suited – although this calls for a level of toxicological information that limits the number of compounds that can be studied simultaneously. Where both were performed, moving from HI to more refined approach produced similar results. In conclusion, both approaches - exposure aggregation and cumulative risk - rely on simple assumptions. Nevertheless, they allow uncertainty to be reduced, in comparison with source-by-source or chemical-by-chemical approaches.
ISSN: 0013-9351

hal-01635759
https://hal.archives-ouvertes.fr/hal-01635759
https://hal.archives-ouvertes.fr/hal-01635759/document
https://hal.archives-ouvertes.fr/hal-01635759/file/Pelletier%202017%20Review%20%20rev2.pdf
DOI : 10.1016/j.envres.2017.06.022

Éditeur(s) : Elsevier
Résumé : Introduction of non-indigenous species can alter marine communities and ecosystems. In shellfish farming, transfer of livestock, especially oysters, is a common practice and potentially constitutes a pathway for non-indigenous introductions. Many species of seaweeds are believed to have been accidentally introduced in association with these transfers, but there is little direct evidence. We experimentally simulated the transfer of oysters from the Thau Lagoon (France). These transfers involved increasing periods of aerial emersion and additional brine and hot water treatments. The brine and hot water treatments were evaluated as a means of reducing the probability of algal introductions with oyster transfers. Shells were cultured for 40 days in experimental tanks to identify the macroalgae likely to be introduced with any oyster transfer. A total of 57 macroalgal taxa, including 16 taxa not indigenous to the Thau Lagoon, were recorded across all treatments and experiments. The abundance of some species increased in several cases following aerial emersion. Elimination treatments (immersion in brine or hot water) significantly reduced algal diversity, with hot water treatments resulting in no species or only tubular Ulva spp. present. The results support the hypothesis that oyster transfers are effective as primary and secondary vectors of macroalgal introductions. Relatively simple changes to the transfer practice (particularly hot water treatments) are suggested as a means of reducing the risk of non-indigenous algal introductions.
Biological Conservation (0006-3207) (Elsevier), 2007-06 , Vol. 137 , N. 2 , P. 237-247

Droits : 2007 Elsevier Ltd All rights reserved.
http://archimer.ifremer.fr/doc/2007/publication-2779.pdf
DOI:10.1016/j.biocon.2007.02.001
http://archimer.ifremer.fr/doc/00000/2779/

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: The Hippo pathway regulates growth rate and organ size in fly and mouse, notably through control of cell proliferation. Molecular interactions at the heart of this pathway are known to have originated in the unicellular ancestry of metazoans. They notably involve a cascade of phosphorylations triggered by the kinase Hippo, with sub‑ sequent nuclear to cytoplasmic shift of Yorkie localisation, preventing its binding to the transcription factor Scalloped, thereby silencing proliferation genes. There are few comparative expression data of Hippo pathway genes in non‑ model animal species and notably none in non‑bilaterian phyla.Results: All core Hippo pathway genes could be retrieved from the ctenophore Pleurobrachia pileus and the hydro‑ zoan cnidarian Clytia hemisphaerica, with the important exception of Yorkie in ctenophore. Expression study of the Hippo, Salvador and Scalloped genes in tentacle " cellular conveyor belts " of these two organisms revealed striking differences. In P. pileus, their transcripts were detected in areas where undifferentiated progenitors intensely prolifer‑ ate and where expression of cyclins B and D was also seen. In C. hemisphaerica, these three genes and Yorkie are expressed not only in the proliferating but also in the differentiation zone of the tentacle bulb and in mature tentacle cells. However, using an antibody designed against the C. hemiphaerica Yorkie protein, we show in two distinct cell lineages of the medusa that Yorkie localisation is predominantly nuclear in areas of active cell proliferation and mainly cytoplasmic elsewhere.Conclusions: This is the first evidence of nucleocytoplasmic Yorkie shift in association with the arrest of cell prolifera‑ tion in a cnidarian, strongly evoking the cell division‑promoting role of this protein and its inhibition by the activated Hippo pathway in bilaterian models. Our results furthermore highlight important differences in terms of deployment and regulation of Hippo pathway genes between cnidarians and ctenophores.
ISSN: 2041-9139

Droits : http://creativecommons.org/licenses/by/
hal-01286578
http://hal.upmc.fr/hal-01286578
http://hal.upmc.fr/hal-01286578/document
http://hal.upmc.fr/hal-01286578/file/comparative.pdf
DOI : 10.1186/s13227-016-0041-y

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
The retroviral genome consists of an intron-containing transcript that has essential cytoplasmic functions in the infected cell. This viral transcript can escape splicing, circumvent the nuclear checkpoint mechanisms and be transported to the cytoplasm by hijacking the host machinery. Once in the cytoplasm, viral unspliced RNA acts as mRNA to be translated and as genomic RNA to be packaged into nascent viruses. The murine leukemia virus (MLV) is among the first retroviruses discovered and is classified as simple Retroviridae due to its minimal encoding capacity. The oncogenic and transduction abilities of MLV are extensively studied, whereas surprisingly the crucial step of its nuclear export has remained unsolved until 2014. Recent work has revealed the recruitment by MLV of the cellular NXF1/Tap-dependent pathway for export. Unconventionally, MLV uses of Tap to export both spliced and unspliced viral RNAs. Unlike other retroviruses, MLV does not harbor a unique RNA signal for export. Indeed, multiple sequences throughout the MLV genome appear to promote export of the unspliced MLV RNA. We review here the current understanding of the export mechanism and highlight the determinants that influence MLV export. As the molecular mechanism of MLV export is elucidated, we will gain insight into the contribution of the export pathway to the cytoplasmic fate of the viral RNA
ISSN: 1547-6286

hal-01217990
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217990
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217990/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217990/file/Insights%20into%20the%20nuclear%20export%20of%20murine%20leukemia%20virus%20intron-containing%20RNA.pdf
DOI : 10.1080/15476286.2015.1065375

Éditeur(s) : Elsevier
Résumé : During the Fanindien 2006 cruise of R/V 'Beautemps-Beaupre', high resolution multibeam bathymetry, sub-bottom profiling and sediment coring was carried out along the East African margin, offshore Tanzania and Mozambique (Indian Ocean). The newly acquired data reveal the presence of a giant deep-sea valley (the Tanzania channel) that is more than 10 km wide at 4000 m water depth, along the continental rise. The valley remains similar to 70 m deep and 7 km wide at 800 km from the Tanzania coast. Morphological comparison with worldwide submarine channels show that the Tanzania channel is one of the largest known submarine valleys. This discovery brings new light on development of submarine valleys that drain sediments originated from the East African Rift System (EARS) highlands (i.e. the Tanzania channel and its neighbor Zambezi channel located similar to 1000 km southward). Both of the systems have a morphology markedly different to the classical sinuous, V-shaped channels located at similar latitudes (e.g. the Zaire or Amazon channels). Their submarine drainage system consists of a downslope converging tributary canyons joining a central trunk channel in the continental rise. The presence of such giant deep-sea drainage systems is probably linked to a strong structural control on the sediment pathway, associated to a massive sediment transfer towards the Indian Ocean in relation with the tectonic activity of the East African Rift System (i.e. the uplift periods trough mid-Miocene and Plio-Pleistocene times) and its interplay with the East African equatorial climate changes.
Marine Geology (0025-3227) (Elsevier), 2008-12 , Vol. 255 , N. 3-4 , P. 179-185

Droits : 2008 Elsevier B.V. All rights reserved.
http://archimer.ifremer.fr/doc/00324/43491/42958.pdf
DOI:10.1016/j.margeo.2008.09.002
http://archimer.ifremer.fr/doc/00324/43491/

Éditeur(s) : HAL CCSD BioScientifica
Résumé : International audience
The general rules established from mammalian species for the regulation of spermatogenesis by gonadotropins may not be fully relevant in fish. Particularly, Fsh is as potent as Lh to stimulate steroidogenesis and the Fsh receptor is expressed in Leydig cells. In seasonal breeders, Fsh is likely the major gonadotropin involved in spermatogenesis onset and Lh is required to support spermatogenesis progression and gamete release. However, the genes that relay the action of Fsh and Lh have been poorly investigated in fish. The present study was aimed at identifying gonadotropin-dependent genes expressed in the testis during fish puberty. We cultured pubertal trout testicular explants for 96 h, with or without gonadotropin, and analyzed transcriptome variations using microarrays. Fsh and Lh had similar effects on a large group of genes while other genes were preferentially regulated by one or the other gonadotropin. We showed that most of the responsive genes were expressed in somatic cells and exhibited relevant patterns during the seasonal reproductive cycle. Some genes preferentially modulated by Lh could be involved in testicular cell fate (pvrl1 and bty) or sperm maturation (ehmt2 and racgap1) and will deserve further examination. Besides Fsh's effects on the steroidogenic pathway, our study demonstrates that Fsh coordinates relevant stimulatory and inhibitory paracrine factors known to regulate early germ cell proliferation and differentiation. Some of these genes belong to major regulatory pathways including the Igf pathway (igf1b/igf3 and igfbp6), the Tgfb pathway (amh, inha, inhba, and fstl3), the Wnt pathway (wisp1), and pleiotrophin (mdka).
ISSN: 0952-5041

inserm-00812401
http://www.hal.inserm.fr/inserm-00812401
DOI : 10.1530/JME-12-0197
PUBMED : 23045716

Éditeur(s) : Elsevier Sci Ltd
Résumé : Many questions remain unanswered regarding RNAi-based mechanisms and dsRNA-induced antiviral immune responses in penaeid shrimp. In this study, we report the characterization in the white leg shrimp Litopenaeus vannamei of RNAi pathway associated proteins Lv-Ago 1 and Lv-Ago 2, two members of the Argonaute family of proteins, as well as Lv-sid 1, the first shrimp homologue of Sid-1, a membrane channel-forming protein implicated in the cellular import of dsRNA. To decipher their functional implication in RNAi-related phenomena, we monitored their relative expression following stimulation by specific and non-specific RNA duplexes of diverse length. The findings show that the length of small RNA duplexes plays a critical role in the activation of both RNAi-related and innate antiviral responses. They also suggest that these two mechanisms of antiviral response may activate the same pathway, requiring Lv-Sid 1 and Lv-Ago 2 induction. (C) 2010 Elsevier Ltd. All rights reserved.
Developmental And Comparative Immunology (0145-305X) (Elsevier Sci Ltd), 2010-11 , Vol. 34 , N. 11 , P. 1209-1218

Droits : 2010 Elsevier Ltd All rights reserved.
http://archimer.ifremer.fr/doc/00015/12652/9587.pdf
DOI:10.1016/j.dci.2010.06.017
http://archimer.ifremer.fr/doc/00015/12652/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Mitochondrial DNA integrity is ensured by several nuclear-encoded proteins in vertebrates, and a number of mtDNA alterations in human diseases, including deletions and duplications, have been suspected to result from errors in the mitochondrial recombination pathway. However, the presence of the latter system is still a matter of controversy as RecA proteins display various functions in vitro. In Escherichia coli, RecA plays a central role in homologous recombination by pairing and transferring a single strand to a homologous duplex DNA. To address indirectly the issue of a mitochondrial recombination pathway in vivo, we have constructed a chimeric gene containing an N terminal mitochondrial targeting sequence and the E. coli RecA gene. Cells were transfected by the recombinant plasmid, then tested for their mtDNA repair upon bleomycin treatment. We found an increased repair rate of the mitochondrial DNA in cells expressing RecA as compared to control cells. These results indicate that the transfected cells display an improved mtDNA repair replication pathway due to the exogenous RecA, likely in synergy with an endogenous rate-limiting mitochondrial recombination pathway.
ISSN: 0027-5107

hal-01680533
https://hal.univ-antilles.fr/hal-01680533
PUBMED : 11356332

Éditeur(s) : Elsevier
Résumé : During the Fanindien 2006 cruise of R/V 'Beautemps-Beaupre', high resolution multibeam bathymetry, sub-bottom profiling and sediment coring was carried out along the East African margin, offshore Tanzania and Mozambique (Indian Ocean). The newly acquired data reveal the presence of a giant deep-sea valley (the Tanzania channel) that is more than 10 km wide at 4000 m water depth, along the continental rise. The valley remains similar to 70 m deep and 7 km wide at 800 km from the Tanzania coast. Morphological comparison with worldwide submarine channels show that the Tanzania channel is one of the largest known submarine valleys. This discovery brings new light on development of submarine valleys that drain sediments originated from the East African Rift System (EARS) highlands (i.e. the Tanzania channel and its neighbor Zambezi channel located similar to 1000 km southward). Both of the systems have a morphology markedly different to the classical sinuous, V-shaped channels located at similar latitudes (e.g. the Zaire or Amazon channels). Their submarine drainage system consists of a downslope converging tributary canyons joining a central trunk channel in the continental rise. The presence of such giant deep-sea drainage systems is probably linked to a strong structural control on the sediment pathway, associated to a massive sediment transfer towards the Indian Ocean in relation with the tectonic activity of the East African Rift System (i.e. the uplift periods trough mid-Miocene and Plio-Pleistocene times) and its interplay with the East African equatorial climate changes. (C) 2008 Elsevier B.V. All rights reserved.
Marine Geology (0025-3227) (Elsevier), 2008-12 , Vol. 255 , N. 3-4 , P. 179-185

Droits : 2008 Elsevier B.V. All rights reserved.
http://archimer.ifremer.fr/doc/2008/publication-6855.pdf
DOI:10.1016/j.margeo.2008.09.002

Éditeur(s) : Elsevier
Résumé : The uptake and loss kinetics of Cd were determined in two species of scallops from the European coasts, the variegated scallop Chlamys varia and the king scallop Pecten maximus, following exposures via seawater, phytoplankton and sediment using highly sensitive radiotracer techniques (Cd-109). Results indicate that, for seawater and dietary pathways, C. varia displays higher bioaccumulation capacities in terms of uptake rate from water and fraction absorbed from ingested food (assimilation efficiency) than Pecten maximus. Regarding sediment exposure, P. maximus displayed low steady-state Cd transfer factor (TFSS < 1); however, once incorporated, a very large part of Cd transferred from sediment (92%) was strongly retained within R maximus tissues. Both species showed a high retention capacity for Cd (biological half-life, T-b1/2 > 4 months), suggesting efficient mechanisms of detoxification and storage in both species. The digestive gland was found to be the main storage organ of Cd in the two scallops regardless of the exposure pathway. However, Cd was stored differently within this organ according to the species considered: 40% of the total Cd was found in the soluble cellular fraction in C. varia whereas this soluble fraction reached 80% for P. maximus. This suggests that the two species displayed different Cd detoxification/storage mechanisms. Finally, the present study has determined the relative contribution of the different exposure pathways to global Cd bioaccumulation for the two scallop species. Results clearly show that for both species, food constitutes the major accumulation pathway, contributing for >99% and 84% of the global Cd bioaccumulation in C. varia and R maximus, respectively. This work confirms the previous assumption, derived from a bibliographic overview, that dietary pathway plays a prevalent role in metal bioaccumulation in Pectinidae. (C) 2007 Elsevier B.V. All rights reserved.
Journal of Experimental Marine Biology and Ecology (0022-0981) (Elsevier), 2007-12 , Vol. 353 , N. 1 , P. 58-67

Droits : 2007 Elsevier B.V. All rights reserved.
http://archimer.ifremer.fr/doc/2007/publication-3581.pdf
DOI:10.1016/j.jembe.2007.09.001
http://archimer.ifremer.fr/doc/00000/3581/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
A recent study suggested that adenosine signaling pathway could promote hemolysis in patients with sickle cell anemia (SCA). This signaling pathway involves several gene coding enzymes for which variants have been described. In this study, we analyzed the genotype-phenotype relationships between functional polymorphisms or polymorphisms associated with altered expression of adenosine pathway genes, namely adenosine deaminase (ada; rs73598374), adenosine A2b receptor (adora2b; rs7208480), adenylyl cyclase6 (adcy6; rs3730071, rs3730070, rs7300155), and hemolytic rate in SCA patients. One hundred and fifty SCA patients were genotyped for adcy6, ada, and adora2b variants as well as alpha-globin gene, a genetic factor known to modulate hemolytic rate. Hematological and biochemical data were obtained at steady-state. Lactate dehydrogenase, aspartate aminotransferase, reticulocytes and total bilirubin were used to calculate a hemolytic index. Genotype-phenotype relationships were investigated using parametric tests and multivariate analysis. SCA patients carrying at least one allele of adcy6 rs3730070-G exhibited lower hemolytic rate than non-carriers in univariate analysis (p=0.006). The presence of adcy6 rs3730070-G variant was associated with a decreased hemolytic rate in adjusted model for age and alpha-thalassemia (p=0.032). Our results support a protective effect of adcy6 rs3730070-G variant on hemolysis in SCA patients.
ISSN: 1079-9796

hal-01668332
https://hal.univ-antilles.fr/hal-01668332
DOI : 10.1016/j.bcmd.2016.02.006

Éditeur(s) : HAL CCSD
Résumé : Scope: TNF-Related Apoptosis-Inducing Ligand (TRAIL) induces apoptosis via the extrinsic death pathway in human colon cancer cells. Short Chain Fatty Acids (SCFA) by contrast induce apoptosis of cancer cells via the intrinsic death pathway. We have previously shown that food-grade dairy propionibacteria induce intrinsic apoptosis of colon cancer cells, via SCFA metabolites (propionate and acetate) acting on mitochondria. We investigate here the possible synergistic pro-apoptotic effect between Propionibacterium freudenreichii and TRAIL. Methods and results: Whole transcriptomic analysis demonstrated that propionibacterial supernatant or propionibacterial SCFA, in combination with TRAIL, increased pro-apoptotic gene expression (TRAIL-R2/DR5) and decreased anti-apoptotic gene expression (FLIPL, XIAP) in HT29 human colon cancer cells. The revealed synergistic pro-apoptotic effect, depending on both death receptors (TRAIL-R1/DR4, TRAIL-R2/DR5) and caspases (caspase-8, -9 and -3) activation, was lethal on cancer cells but not on normal human intestinal epithelial cells (HIEC), and was inhibited by Bcl-2 expression. Finally, milk fermented by P. freudenreichii induced HT29 cells apoptosis and enhanced TRAIL cytotoxic activity, as did P. freudenreichii culture supernatants or its SCFA metabolites.Conclusion: The revealed synergy opens new applications for food-grade P. freudenreichii-containing products as new adjuvants to potentiate TRAIL-based cancer therapy in colorectal cancer.
International Scientific Conference on Probiotics and Prebiotics - IPC2016
Budapest, Hungary

hal-01286497
https://hal.archives-ouvertes.fr/hal-01286497
PRODINRA : 349367

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Estrogen receptors (ER) α and β are found in both women and men in many tissues, where they have different functions, including having roles in cell proliferation and differentiation of the reproductive tract. In addition to estradiol (E2), a natural hormone, numerous compounds are able to bind ERs and modulate their activities. Among these compounds, phytoestrogens such as isoflavones, which are found in plants, are promising therapeutics for several pathologies. Glyceollins are second metabolites of isoflavones that are mainly produced in soybean in response to an elicitor. They have potentially therapeutic actions in breast cancer by reducing the proliferation of cancer cells. However, the molecular mechanisms driving these effects remain elusive. METHODS: First, to determine the proliferative or anti-proliferative effects of glyceollins, in vivo and in vitro approaches were used. The length of epithelial duct in mammary gland as well as uterotrophy after treatment by E2 and glyceollins and their effect on proliferation of different breast cell line were assessed. Secondly, the ability of glyceollin to activate ER was assessed by luciferase assay. Finally, to unravel molecular mechanisms involved by glyceollins, transcriptomic analysis was performed on MCF-7 breast cancer cells. RESULTS: In this study, we show that synthetic versions of glyceollin I and II exert anti-proliferative effects in vivo in mouse mammary glands and in vitro in different ER-positive and ER-negative breast cell lines. Using transcriptomic analysis, we produce for the first time an integrated view of gene regulation in response to glyceollins and reveal that these phytochemicals act through at least two major pathways. One pathway involving FOXM1 and ERα is directly linked to proliferation. The other involves the HIF family and reveals that stress is a potential factor in the anti-proliferative effects of glyceollins due to its role in increasing the expression of REDD1, an mTORC1 inhibitor. CONCLUSION: Overall, our study clearly shows that glyceollins exert anti-proliferative effects by reducing the expression of genes encoding cell cycle and mitosis-associated factors and biomarkers overexpressed in cancers and by increasing the expression of growth arrest-related genes. These results reinforce the therapeutic potential of glyceollins for breast cancer.
ISSN: 1478-811X

hal-01560288
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560288
DOI : 10.1186/s12964-017-0182-1
PUBMED : 28666461

Éditeur(s) : HAL CCSD American Society of Hematology
Résumé : International audience
Polycythemia vera (PV) is characterized by an increased RBC mass, spontaneous erythroid colony formation, and the JAK2V617F mutation. PV is associated with a high risk of mesenteric and cerebral thrombosis. PV RBC adhesion to endothelial laminin is increased and mediated by phosphorylated erythroid Lu/BCAM. In the present work, we investigated the mechanism responsible for Lu/BCAM phosphorylation in the presence of JAK2V617F using HEL and BaF3 cell lines as well as RBCs from patients with PV. High levels of Rap1-GTP were found in HEL and BaF3 cells expressing JAK2V617F compared with BaF3 cells with wild-type JAK2. This finding was associated with increased Akt activity, Lu/BCAM phosphorylation, and cell adhesion to laminin that were inhibited by the dominant-negative Rap1S17N or by the specific Rap1 inhibitor GGTI-298. Surprisingly, knocking-down EpoR in HEL cells did not alter Akt activity or cell adhesion to laminin. Our findings reveal a novel EpoR-independent Rap1/Akt signaling pathway that is activated by JAK2V617F in circulating PV RBCs and responsible for Lu/BCAM activation. This new characteristic of JAK2V617F could play a critical role in initiating abnormal interactions among circulating and endothelial cells in patients with PV.
ISSN: 0006-4971

inserm-00821109
http://www.hal.inserm.fr/inserm-00821109
http://www.hal.inserm.fr/inserm-00821109/document
http://www.hal.inserm.fr/inserm-00821109/file/De_Grandis_Blood_2013.pdf
DOI : 10.1182/blood-2012-07-440487

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Estrogen receptor alpha (ERα) is generally considered to be a good prognostic marker because almost 70% of ERα-positive tumors respond to anti-hormone therapies. Unfortunately, during cancer progression, mammary tumors can escape from estrogen control, resulting in resistance to treatment. In this study, we demonstrate that activation of the actin/megakaryoblastic leukemia 1 (MKL1) signaling pathway promotes the hormonal escape of estrogen-sensitive breast cancer cell lines. The actin/MKL1 signaling pathway is silenced in differentiated ERα-positive breast cancer MCF-7 and T47D cell lines and active in ERα-negative HMT-3522 T4-2 and MDA-MB-231 breast cancer cells, which have undergone epithelial-mesenchymal transition. We showed that MKL1 activation in MCF-7 cells, either by modulating actin dynamics or using MKL1 mutants, down-regulates ERα expression and abolishes E2-dependent cell growth. Interestingly, the constitutively active form of MKL1 represses PR and HER2 expression in these cells and increases the expression of HB-EGF, TGFβ, and amphiregulin growth factors in an E2-independent manner. The resulting expression profile (ER-, PR-, HER2-) typically corresponds to the triple-negative breast cancer expression profile.
ISSN: 0303-7207

hal-01061363
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061363
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061363/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061363/file/Activationsur the_MKL1actin_Kerdivel_et_al._text_Figures.pdf
DOI : 10.1016/j.mce.2014.03.009

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein (MAP) kinase pathway has been involved in the positive and negative regulation of cell proliferation. Upon mitogen stimulation, ERK1/ERK2 activation is necessary for G1- to S-phase progression whereas when hyperactived, this pathway could elicit cell cycle arrest. The mechanisms involved are not fully elucidated but a kinase-independent function of ERK1/2 has been evidenced in the MAPK-induced growth arrest. Here, we show that p70S6K, a central regulator of protein biosynthesis, is essential for the cell cycle arrest induced by overactivation of ERK1/2. Indeed, whereas MEK1 silencing inhibits cell cycle progression, we demonstrate that active mutant form of MEK1 or MEK2 triggers a G1 phase arrest by stimulating an activation of p70S6K by ERK1/2 kinases. Silencing of ERK1/2 activity by shRNA efficiently suppresses p70S6K phosphorylation on Thr421/Ser424 and S6 phosphorylation on Ser240/244 as well as p21 expression, but these effects can be partially reversed by the expression of kinase-dead mutant form of ERK1 or ERK2. In addition, we demonstrate that the kinase p70S6K modulates neither the p21 gene transcription nor the stability of the protein but enhances the translation of the p21 mRNA. In conclusion, our data emphasizes the importance of the translational regulation of p21 by the MEK1/2-ERK1/2-p70S6K pathway to negatively control the cell cycle progression. J. Cell. Physiol. 229: 903-915, 2014. © 2013 Wiley Periodicals, Inc.
ISSN: 0021-9541

hal-01061238
https://hal.archives-ouvertes.fr/hal-01061238
https://hal.archives-ouvertes.fr/hal-01061238/document
https://hal.archives-ouvertes.fr/hal-01061238/file/MEK12_OveractivationArticle_GUEGAN_JCP_2014.pdf
DOI : 10.1002/jcp.24521

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Banana has been a main agricultural product in the French West Indies (Guadeloupe and Martinique) since the 1960s. This crop requires the intensive use of pesticides to prevent attacks by insect pests. Chlorinated pesticides, such as hexachlorocyclohexane (HCH), chlordecone and dieldrin, were used until the beginning of the 1990s, resulting in a generalized diffuse contamination of the soil and water in the areas of banana production, hence the need to develop solutions for cleanup of the polluted sites. The aims of this work were (i) to assess lindane degradation in soil slurry microcosms treated with lindane at 10 mg/L and (ii) to detect the catabolic genes involved in the HCH degradation pathway. The soil slurry microcosm system showed a 40 % lindane degradation efficiency at the end of a 30-day experiment. Lower lindane removal was also detected in the abiotic controls, probably caused by pesticide adsorption to soil particles. Indeed, the lindane concentration decreased from 6000 to 1330 ng/mL and from 800 to 340 ng/mL for the biotic and abiotic soils, respectively. Nevertheless, some of the genes involved in the HCH degradation pathway were amplified by polymerase chain reaction (PCR) from crude deoxyribonucleic acid (DNA) extracted from the Guadeloupe agricultural soil, suggesting that HCH degradation is probably mediated by bacteria closely related to the family Sphingomonadaceae.
ISSN: 0944-1344

hal-01545905
https://hal.archives-ouvertes.fr/hal-01545905
DOI : 10.1007/s11356-015-5875-7

Éditeur(s) : HAL CCSD Springer New York
Résumé : International audience
Estrogen receptor α (ERα) exerts regulatory actions through genomic mechanisms. In the classical pathway, ligand-activated ERα binds directly to DNA through estrogen response elements (ERE) located in the promoter of target genes. ERα can also exert indirect regulation of transcription via protein-protein interaction with other transcription factors such as AP-1. Several ERα synonymous polymorphisms have been identified and efforts to understand their implications have been made. Nevertheless effects of synonymous polymorphisms are still neglected. This chapter focuses on the experimental procedure employed in order to characterize the transcriptional activity of a synonymous polymorphism of the ERα (rs746432) called Alanine 87 (Ala87). Activity of both WT and Ala87 ERα isoforms on transcriptional pathways can be analyzed in transiently transfected cells using different reporter constructs. ERα efficiency on the classical genomic pathway can be analyzed by determining its transactivation activity on an ERE-driven thymidine kinase (TK) promoter controlling the expression of the luciferase reporter gene. Transcriptional activity through the indirect genomic pathway can be analyzed by employing an AP-1 DNA response element-driven promoter also controlling the expression of luciferase reporter gene
Estrogen Receptors

ISBN : 978-1-4939-3126-2
hal-01237073
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237073
DOI : 10.1007/978-1-4939-3127-9_22

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Motility and invasiveness events require specific intracellular signaling cascade activations. In cancer liver cells, one of these mechanisms could involve the MAPK MEK/ERK cascade activation which has been shown over expressed and activated in hepatocellular carcinoma. To study whether the MEK/ERK cascade is involved in the motility of HCC, we examined the effect of MEK inhibitor and ERK2 silencing using monolayer wound-healing assays and fluoroblock invasion systems. Evidence was provided that the MAPK cascade is a key transduction pathway which controls HCC cells motility and invasiveness. We could disconnect proliferation to motility using mitomycin C and we established that RNAi-mediated inhibition of ERK2 led to strongly reduced cell motility. To improve our understanding, we analysed the regulation and the role of urokinase receptor (uPAR) in this process. We provided evidence that uPAR was under a MEK/ERK dependent mechanism and blocking uPAR activity using specific antagonist or inhibiting its expression by RNA interference which resulted in complete inhibition of motility. Moreover, we found in MAPK inhibited cultures and in uPAR silencing cells that p70S6K phosphorylation on residue Thr-389 was significantly reduced, whereas Ser-421/Thr-424 phosphorylation did not change. We highlighted that the FRAP/mTOR pathway did not affect motility and Thr-389 phosphorylation. Furthermore, we demonstrated that p70S6K inhibition by RNA interference completely inhibited hepatocarcinoma cell motility. Therefore, targeting uPAR and/or MEK/ERK/S6K by RNA interference could be a major therapeutic strategy for the future treatment of invasive hepatocarcinoma cells.
ISSN: 0021-9541

hal-00697044
https://hal.archives-ouvertes.fr/hal-00697044
DOI : 10.1002/jcp.21049
PUBMED : 17427199

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
A set of four reactive flow-through experiments at temperature T = 100 degrees C and total pressure P=12 MPa was performed in limestone reservoir samples. By using various ranging from 0.7 to 10 MPa, these experiments mimic mass transfers occurring (1) near the injection well, where the brine is almost saturated with CO2 (i.e. P-CO2 approximate to P), and (2) at increasing distances from the injection well, where the fluid displays lower values and higher divalent cation concentrations due rock dissolution along the fluid pathway. Results for P-CO2 = 10 MPa show non-uniform dissolution features associated with transport-controlled mass transfer, while reaction-controlled uniform dissolution is observed for P-CO2 = 2.5 MPa. The experiment with P-CO2 = 6 MPa allows investigating in detail the transition from transport-to reaction-controlled dissolution. Conversely, the experiment reproducing conditions far from the injection well (P-CO2 = 0.7 MPa), shows a decrease of porosity triggered by the precipitation of Mg-rich calcite. For all the dissolution experiments, the time-resolved porosity phi(t) can be modeled by a simple non-linear equation including parameters that characterise the dissolution regime triggered by the reactivity of the inlet fluid (measured by the Damkohler number, Da). Furthermore, all dissolution experiments display power scaling between permeability (k) and porosity (phi) with distinctly different scaling exponents characterising the reactivity of the fluid percolating the sample, independently from the decrease with time of the reactive surface area. It is shown also that dissolution at moderate positive values of Da seems the most efficient to increase permeability and promote a rapid spreading of the reaction front, while inducing minimal modification of the porosity in the vicinity of the CO2 injection well. These results can be used to parameterize the k-phi function for modeling the earliest dissolution processes occurring in the vicinity of the reaction front.
ISSN: 0009-2541

hal-00445277
https://hal.archives-ouvertes.fr/hal-00445277
DOI : 10.1016/j.chemgeo.2009.03.028