Publications by authors named "Catherine Rey"

13 Publications

  • Page 1 of 1

Uncovering the Translational Regulatory Activity of the Tumor Suppressor BRCA1.

Cells 2020 04 10;9(4). Epub 2020 Apr 10.

Inserm U1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Université de Lyon 1, Centre Léon Bérard, F-69008 Lyon, France.

BRCA1 inactivation is a hallmark of familial breast cancer, often associated with aggressive triple negative breast cancers. BRCA1 is a tumor suppressor with known functions in DNA repair, transcription regulation, cell cycle control, and apoptosis. In the present study, we demonstrate that BRCA1 is also a translational regulator. We previously showed that BRCA1 was implicated in translation regulation. Here, we asked whether translational control could be a novel function of BRCA1 that contributes to its tumor suppressive activity. A combination of RNA-binding protein immunoprecipitation, microarray analysis, and polysome profiling, was used to identify the mRNAs that were specifically deregulated under BRCA1 deficiency. Western blot analysis allowed us to confirm at the protein level the deregulated translation of a subset of mRNAs. A unique and dedicated cohort of patients with documented germ-line BRCA1 pathogenic variant statues was set up, and tissue microarrays with the biopsies of these patients were constructed and analyzed by immunohistochemistry for their content in each candidate protein. Here, we show that BRCA1 translationally regulates a subset of mRNAs with which it associates. These mRNAs code for proteins involved in major programs in cancer. Accordingly, the level of these key proteins is correlated with BRCA1 status in breast cancer cell lines and in patient breast tumors. ADAT2, one of these key proteins, is proposed as a predictive biomarker of efficacy of treatments recently recommended to patients with BRCA1 deficiency. This study proposes that translational control may represent a novel molecular mechanism with potential clinical impact through which BRCA1 is a tumor suppressor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cells9040941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226996PMC
April 2020

Deregulation of miR-183 and KIAA0101 in Aggressive and Malignant Pituitary Tumors.

Front Med (Lausanne) 2015 10;2:54. Epub 2015 Aug 10.

Centre de Recherche en Cancérologie de Lyon, INSERM U1052/CNRS UMR 5286 Centre Léon Bérard , Lyon , France ; Université Lyon 1, Université de Lyon , Lyon , France ; ProfileXpert, SFR-Est, CNRS UMR-S3453, INSERM US7 , Lyon , France.

Changes in microRNAs (miRNAs) expression in many types of cancer suggest that they may be involved in crucial steps during tumor progression. Indeed, miRNAs deregulation has been described in pituitary tumorigenesis, but few studies have described their role in pituitary tumor progression toward aggressiveness and malignancy. To assess the role of miRNAs within the hierarchical cascade of events in prolactin (PRL) tumors during progression, we used an integrative genomic approach to associate clinical-pathological features, global miRNA expression, and transcriptomic profiles of the same human tumors. We describe the specific down-regulation of one principal miRNA, miR-183, in the 8 aggressive (A, grade 2b) compared to the 18 non-aggressive (NA, grades 1a, 2a) PRL tumors. We demonstrate that it acts as an anti-proliferative gene by directly targeting KIAA0101, which is involved in cell cycle activation and inhibition of p53-p21-mediated cell cycle arrest. Moreover, we show that miR-183 and KIAA0101 expression significantly correlate with the main markers of pituitary tumors aggressiveness, Ki-67 and p53. These results confirm the activation of proliferation in aggressive and malignant PRL tumors compared to non-aggressive ones. Importantly, these data also demonstrate the ability of such an integrative genomic strategy, applied in the same human tumors, to identify the molecular mechanisms responsible for tumoral progression even from a small cohort of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2015.00054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530307PMC
August 2015

The workflow from post-mortem human brain sampling to cell microdissection: a Brain Net Europe study.

J Neural Transm (Vienna) 2015 Jul 16;122(7):975-91. Epub 2015 May 16.

INSERM U1028; CNRS UM5292; Lyon Neuroscience Research Center, Neuro-oncology and Neuro-inflammation Team, 69000, Lyon, France,

Brain banks manage and store fully clinically and pathologically characterised brains. The diversity of techniques used in research projects increases. These biological resource centres are made to adapt brain tissue processing. Furthermore, the development of more sensitive techniques to analyse nucleic acids and proteins offers new fields of exploration when combined with laser capture microdissection in order to decipher the physiopathology of diseases at the cell level. In this study, our goal was to evaluate procedures and set a workflow compatible with the constraints of brain banks, from brain sampling to laser capture microdissection and pre-analytical quality assessment. We compared various methods of freezing brain tissue, focused on morphological quality preservation of brain microscopical structures and on the quality of nucleic acid or protein yields. Staining protocols combined with strategies to lower neurones autofluorescence were adapted for the same purpose. Finally, we found that laser capture microdissection is possible in the setting of brain banks. However, the entire process has to be envisioned from the autopsy to the analysis. The impact on protein or nucleic acid quality is a limitation that restricts the amount of samples available for this purpose.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00702-015-1378-4DOI Listing
July 2015

Detection and genetic characterization of Seoul virus from commensal brown rats in France.

Virol J 2014 Feb 20;11:32. Epub 2014 Feb 20.

Université de Lyon, VetAgro Sup, USC 1233/Equipe « Pathogènes émergents et rongeurs sauvages (PERS), F-69280 Marcy-L'Etoile, France.

Background: Hantaviruses are single-stranded RNA viruses, which are transmitted to humans primarily via inhalation of aerosolised virus in contaminated rodent urine and faeces. Whilst infected reservoir hosts are asymptomatic, human infections can lead to two clinical manifestations, haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS), with varying degrees of clinical severity. The incidence of rodent and human cases of Seoul virus (SEOV) in Europe has been considered to be low, and speculated to be driven by the sporadic introduction of infected brown rats (Rattus norvegicus) via ports.

Methods: Between October 2010 and March 2012, 128 brown rats were caught at sites across the Lyon region in France.

Results: SEOV RNA was detected in the lungs of 14% (95% CI 8.01-20.11) of brown rats tested using a nested pan-hantavirus RT-PCR (polymerase gene). Phylogenetic analysis supports the inclusion of the Lyon SEOV within Lineage 7 with SEOV strains originating from SE Asia and the previously reported French & Belgian SEOV strains. Sequence data obtained from the recent human SEOV case (Replonges) was most similar to that obtained from one brown rat trapped in a public park in Lyon city centre. We obtained significantly improved recovery of virus genome sequence directly from SEOV infected lung material using a simple viral enrichment approach and NGS technology.

Conclusions: The detection of SEOV in two wild caught brown rats in the UK and the multiple detection of SEOV infected brown rats in the Lyon region of France, suggests that SEOV is circulating in European brown rats. Under-reporting and difficulties in identifying the hantaviruses associated with HFRS may mask the public health impact of SEOV in Europe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1743-422X-11-32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944734PMC
February 2014

In vitro and in vivo models of cerebral ischemia show discrepancy in therapeutic effects of M2 macrophages.

PLoS One 2013 25;8(6):e67063. Epub 2013 Jun 25.

CNRS, UMR 5220; INSERM, U1044; INSA de Lyon, France.

THE INFLAMMATORY RESPONSE FOLLOWING ISCHEMIC STROKE IS DOMINATED BY INNATE IMMUNE CELLS: resident microglia and blood-derived macrophages. The ambivalent role of these cells in stroke outcome might be explained in part by the acquisition of distinct functional phenotypes: classically (M1) and alternatively activated (M2) macrophages. To shed light on the crosstalk between hypoxic neurons and macrophages, an in vitro model was set up in which bone marrow-derived macrophages were co-cultured with hippocampal slices subjected to oxygen and glucose deprivation. The results showed that macrophages provided potent protection against neuron cell loss through a paracrine mechanism, and that they expressed M2-type alternative polarization. These findings raised the possibility of using bone marrow-derived M2 macrophages in cellular therapy for stroke. Therefore, 2 million M2 macrophages (or vehicle) were intravenously administered during the subacute stage of ischemia (D4) in a model of transient middle cerebral artery occlusion. Functional neuroscores and magnetic resonance imaging endpoints (infarct volumes, blood-brain barrier integrity, phagocytic activity assessed by iron oxide uptake) were longitudinally monitored for 2 weeks. This cell-based treatment did not significantly improve any outcome measure compared with vehicle, suggesting that this strategy is not relevant to stroke therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0067063PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3692438PMC
February 2014

The absence of melanopsin alters retinal clock function and dopamine regulation by light.

Cell Mol Life Sci 2013 Sep 19;70(18):3435-47. Epub 2013 Apr 19.

Department of Chronobiology, INSERM U846, Stem Cell and Brain Research Institute, 18 Avenue du Doyen Lépine, 69500, Bron, France.

The retinal circadian clock is crucial for optimal regulation of retinal physiology and function, yet its cellular location in mammals is still controversial. We used laser microdissection to investigate the circadian profiles and phase relations of clock gene expression and Period gene induction by light in the isolated outer (rods/cones) and inner (inner nuclear and ganglion cell layers) regions in wild-type and melanopsin-knockout (Opn 4 (-/-) ) mouse retinas. In the wild-type mouse, all clock genes are rhythmically expressed in the photoreceptor layer but not in the inner retina. For clock genes that are rhythmic in both retinal compartments, the circadian profiles are out of phase. These results are consistent with the view that photoreceptors are a potential site of circadian rhythm generation. In mice lacking melanopsin, we found an unexpected loss of clock gene rhythms and of the photic induction of Per1-Per2 mRNAs only in the outer retina. Since melanopsin ganglion cells are known to provide a feed-back signalling pathway for photic information to dopaminergic cells, we further examined dopamine (DA) synthesis in Opn 4 (-/-) mice. The lack of melanopsin prevented the light-dependent increase of tyrosine hydroxylase (TH) mRNA and of DA and, in constant darkness, led to comparatively high levels of both components. These results suggest that melanopsin is required for molecular clock function and DA regulation in the retina, and that Period gene induction by light is mediated by a melanopsin-dependent, DA-driven signal acting on retinal photoreceptors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00018-013-1338-9DOI Listing
September 2013

Complexity and developmental changes in the expression pattern of claudins at the blood-CSF barrier.

Histochem Cell Biol 2012 Dec 11;138(6):861-79. Epub 2012 Aug 11.

Inserm U1028, CNRS UMR 5292, Lyon Neuroscience Research Center, Lyon-1 University, 69008 Lyon, France.

The choroid plexus epithelium controls the movement of solutes between the blood and the cerebrospinal fluid. It has been considered as a functionally more immature interface during brain development than in adult. The anatomical basis of this barrier is the interepithelial choroidal junction whose tightness has been attributed to the presence of claudins. We used quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry to identify different claudins in the choroid plexuses of developing and adult rats. Claudin-1, -2, and -3 were highly and selectively expressed in the choroid plexus as compared to brain or parenchyma microvessels and were localized at epithelial junctions. Claudin-6, -9, -19, and -22 also displayed a previously undescribed choroidal selectivity, while claudin-4, -5, and -16 were enriched in the cerebral microvessels. The choroidal pattern of tight junction protein expression in prenatal brains was already complex and included occludin and zonula occludens proteins. It differed from the adult pattern in that the pore-forming claudin-2, claudin-9, and claudin-22 increased during development, while claudin-3 and claudin-6 decreased. Claudin-2 and claudin-11 presented a mirror image of abundance between lateral ventricle and fourth ventricle choroid plexuses. Imunohistochemical analysis of human fetal and postnatal brains for claudin-1, -2, and -3 demonstrated their early presence and localization at the apico-lateral border of the choroid plexus epithelial cells. Overall, choroidal epithelial tight junctions are already complex in developing brain. The observed differences in claudin expression between developing and adult choroid plexuses may indicate developmental differences in selective blood-cerebrospinal fluid transport functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00418-012-1001-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483103PMC
December 2012

Integrated genomic profiling identifies loss of chromosome 11p impacting transcriptomic activity in aggressive pituitary PRL tumors.

Brain Pathol 2011 Sep 23;21(5):533-43. Epub 2011 Feb 23.

INSERM, U842, Lyon, France.

Integrative genomics approaches associating DNA structure and transcriptomic analysis should allow the identification of cascades of events relating to tumor aggressiveness. While different genome alterations have been identified in pituitary tumors, none have ever been correlated with the aggressiveness. This study focused on one subtype of pituitary tumor, the prolactin (PRL) pituitary tumors, to identify molecular events associated with the aggressive and malignant phenotypes. We combined a comparative genomic hybridization and transcriptomic analysis of 13 PRL tumors classified as nonaggressive or aggressive. Allelic loss within the p arm region of chromosome 11 was detected in five of the aggressive tumors. Allelic loss in the 11q arm was observed in three of these five tumors, all three of which were considered as malignant based on the occurrence of metastases. Comparison of genomic and transcriptomic data showed that allelic loss impacted upon the expression of genes located in the imbalanced region. Data filtering allowed us to highlight five deregulated genes (DGKZ, CD44, TSG101, GTF2H1, HTATIP2), within the missing 11p region, potentially responsible for triggering the aggressive and malignant phenotypes of PRL tumors. Our combined genomic and transcriptomic analysis underlines the importance of chromosome allelic loss in determining the aggressiveness and malignancy of tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1750-3639.2011.00476.xDOI Listing
September 2011

TWIST microdeletion identified by array CGH in a patient presenting Saethre-Chotzen phenotype and a complex rearrangement involving chromosomes 2 and 7.

Eur J Med Genet 2008 Mar-Apr;51(2):156-64. Epub 2007 Dec 24.

Hospices Civils de Lyon, Service de Cytogénétique Constitutionnelle - Centre de Biologie et de Pathologie Est, 59 Boulevard Pinel, Bron 69677 Cedex, France.

Saethre-Chotzen syndrome (SCS), also known as acrocephalosyndactyly III, is an autosomal dominant hereditary disorder characterized by craniofacial and limb anomalies. SCS is generally caused by mutations in the TWIST gene, but several 7p21.3 microdeletions involving the entire gene have also been described. The patient reported here presented with craniosynostosis, ptosis, brachydactyly and syndactyly of toes. Standard lymphocyte karyotype showed a de novo apparently balanced but complex constitution with a translocation between the short arms of chromosomes 2 and 7 and an insertion of the 7(q21.3q22) band in the short arm of the same chromosome 7. Interestingly, array CGH displayed a unique 690 kb deletion in 7p21.3 involving the TWIST gene, consistent with the phenotype. This case illustrates the important contribution of array CGH to identification of complex chromosomal rearrangements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmg.2007.12.003DOI Listing
June 2008

A diagnostic marker set for invasion, proliferation, and aggressiveness of prolactin pituitary tumors.

Endocr Relat Cancer 2007 Sep;14(3):887-900

INSERM, U842, Lyon F-69372 France.

Although most pituitary tumors are benign, some are invasive or aggressive. In the absence of specific markers of malignancy, only tumors with metastases are considered malignant. To identify markers of invasion and aggressiveness, we focused on prolactin (PRL) tumors in the human and rat. Using radiology and histological methods, we classified 25 human PRL tumors into three groups (non-invasive, invasive, and aggressive-invasive) and compared them with a model of transplantable rat PRL tumors with benign and malignant lineages. Combining histological(mitoses and labeling for Ki-67, P53, pituitary transforming tumor gene (PTTG), and polysialic acid neural cell adhesion molecule) and transcriptomic (microarrays and q-RTPCR) methods with clinical data (post-surgical outcome with case-control statistical analysis), we found nine genes implicated in invasion (ADAMTS6, CRMP1, and DCAMKL3) proliferation (PTTG, ASK, CCNB1, AURKB, and CENPE), or pituitary differentiation (PITX1) showing differential expression in the three groups of tumors (P = 0.015 to 0.0001). A case-control analysis, comparing patients in remission (9 controls) and patients with persistent or recurrent tumors (14 cases) revealed that eight out of the nine genes were differentially up- or downregulated (P = 0.05 to 0.002), with only PTTG showing no correlation with clinical course (P = 0.258). These combined histological and transcriptomic analyses improve the pathological diagnosis of PRL tumors, indicating a reliable procedure for predicting tumor aggressiveness and recurrence potential. The similar gene profiles found between non-invasive human and benign rat tumors, as well as between aggressive-invasive human and malignant rat tumors provide new insights into malignancy in human pituitary tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1677/ERC-07-0062DOI Listing
September 2007

Identification of differentially expressed genes in human pineal parenchymal tumors by microarray analysis.

Acta Neuropathol 2005 Mar 31;109(3):306-13. Epub 2004 Dec 31.

INSERM U433, Faculté de Médecine RTH Laennec, 69372, Lyon Cedex 08, France.

Human pineal parenchymal tumors (PPTs) are rare tumors, and little is known about their molecular pathogenesis. We used Atlas plastic human 8 K microarray analysis to identify the genes expressed in four human PPTs of different grades, in normal brain tissue and in a normal fetal pineal gland. We selected the most highly expressed genes in PPT (n=39) and compared their expression to that both in normal brain and fetal pineal gland. Nine genes were expressed more than twice as strongly and 3 at about half the level in PPT. Furthermore, real-time reverse transcription-PCR was performed to compare mRNA levels in the four PPTs, in four medulloblastomas (MBs) (the most common type of similar embryonal neoplasm in the cerebellum), and in normal brain, for 9 of the 39 genes. Among genes showing an expression similar to that obtained with microarray, puromycin-sensitive aminopeptidase and teratocarcinoma-derived growth factor 3 were up-regulated in PPT and in MB, and adenomatous polyposis coli like was down-regulated only in PPT. Up-regulated expression of chromosome 17 open reading frame 1A was seen in high-grade PPT and in MB, but not in lower grade PPT. In conclusion, our results identified a number of genes that are differentially expressed in PPT and MB, and some of them may serve as prognostic markers and can be used to define mechanisms of tumorigenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00401-004-0964-6DOI Listing
March 2005

Expression of somatostatin receptor type-2 (sst2A) in immature porcine Leydig cells and a possible role in the local control of testosterone secretion.

Reprod Biol Endocrinol 2003 Feb 11;1:19. Epub 2003 Feb 11.

Institut National de la Santé et de la Recherche Médicale U-407, France.

We recently reported that immature porcine Leydig cells express both somatostatin (SRIF) and SRIF receptor type-2 (sst-2) transcripts. The present study was therefore undertaken to assess whether SRIF might exert autocrine actions on these cells through sst2A receptor, one of the two sst2 isoforms known to exert important neuroendocrine and endocrine functions. Using a polyclonal antibody directed towards the C-terminal tail of the sst2A receptor subtype, receptor immunoreactivity was detected in a subpopulation of Leydig cells and spermatogonia. To address the physiological correlates of this expression we then studied the possible involvement of sst2 receptor in the regulation of testosterone secretion. Functional assays showed that the sst2 agonist octreotide inhibited both basal and hCG-stimulated testosterone secretion by testosterone pretreated Leydig cells. To assess whether sst2 receptor expression might be regulated by testosterone, we performed a semi-quantitative RT-PCR analysis of sst2 mRNA expression in Leydig cells cultured in the presence or in the absence of the androgen. A significant increase in sst2 receptor transcripts was observed in testosterone-treated cells. Taken together, these data suggest that SRIF can inhibit testosterone secretion through the sst2A receptor. The mechanism of the local inhibitory actions of SRIF is probably autocrine since immature porcine Leydig cells express SRIF itself and it might involve testosterone-induced increase of sst2 receptor expression in immature Leydig cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC151791PMC
http://dx.doi.org/10.1186/1477-7827-1-19DOI Listing
February 2003

Proteomics analysis of cellular response to oxidative stress. Evidence for in vivo overoxidation of peroxiredoxins at their active site.

J Biol Chem 2002 May 19;277(22):19396-401. Epub 2002 Mar 19.

CEA-Laboratoire de Bioénergétique Cellulaire et Pathologique, EA UJF 2943, DRDC/BECP, CEA-Grenoble, 17 rue des martyrs, F-38054 Grenoble Cedex 9, France.

The proteomics analysis reported here shows that a major cellular response to oxidative stress is the modification of several peroxiredoxins. An acidic form of the peroxiredoxins appeared to be systematically increased under oxidative stress conditions. Peroxiredoxins are enzymes catalyzing the destruction of peroxides. In doing so, a reactive cysteine in the peroxiredoxin active site is weakly oxidized (disulfide or sulfenic acid) by the destroyed peroxides. Cellular thiols (e.g. thioredoxin) are used to regenerate the peroxiredoxins to their active state. Tandem mass spectrometry was carried out to characterize the modified form of the protein produced in vivo by oxidative stress. The cysteine present in the active site was shown to be oxidized into cysteic acid, leading to an inactivated form of peroxiredoxin. This strongly suggested that peroxiredoxins behave as a dam upon oxidative stress, being both important peroxide-destroying enzymes and peroxide targets. Results obtained in a primary culture of Leydig cells challenged with tumor necrosis factor alpha suggested that this oxidized/native balance of peroxiredoxin 2 may play an active role in resistance or susceptibility to tumor necrosis factor alpha-induced apoptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.M106585200DOI Listing
May 2002