Cancer du sein et micro-environnement tumoral: rôle de la protéase ...

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Beaujouin, Figure Sup. 2cath-D-/-MEF-cath-DLRP1 siRNA4aLuc siRNAbesiRNALucsiRNA4LRP1LRP1bbactincdFigure Sup. 2. Silencing LRP1 in cath-D expressing MEFs inhibitsinvasive growthcath-D-/-MEF-cath-D cells transfected with LRP1 siRNA4 (panels a andc) or Luc siRNA (panels b and d) were embedded in Matrigel 24 h posttransfection,and analyzed as described in the legend to Figure 6A.
Beaujouin, Figure Sup. 3Luc siRNA HMF co-cultured ona3Y1Ad12/controlb3Y1Ad12/cath-DeHMFsiRNALucsiRNA2LRP1LRP1bbactincLRP1 siRNA2 HMF co-cultured on3Y1Ad12/control 3Y1Ad12/cath-DdfLuc siRNAHMFLRP1 siRNA2HMF- NS52Kpro-cath-DFigure Sup. 3. LRP1 silencing in HMF fibroblasts prevents cath-D-induced outgrowthHMF fibroblasts transfected with Luc siRNA (panels a, b) or LRP1 siRNA2 (panels c, d)were embedded 48h post-transfection in the presence of a bottom layer of 3Y1-Ad12cancer cell lines secreting either no cath-D (control, panels a and c) or human cath-D (cath-D, panels b and d). Phase contrast optical photomicrographs of HMF fibroblasts after 3days of co-culture are shown in panels a-d. HMF cells were transfected with Luc siRNA orLRP1 siRNA2 and LRP1b expression was monitored 48h post-transfection and before theco-culture assays (panel e). Pro-cath-D secretion was analyzed after 3 days of co-cultureof Luc (panel f, left panel) or LRP1 (panel f, right panel) siRNA HMF fibroblasts with3Y1Ad12/control or 3Y1Ad12/cath-D cells by immunoblotting. NS = non-specificcontaminant protein. Bars, 75 µm.
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Université Montpellier I UFR Méd
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Un grand merci à tous mes collabor
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TitleBreast cancer and tumoral micr
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Cancer du sein et micro-environneme
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C. PRESENTATION DU TRAVAIL DE THESE
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But de la thèseLa cathepsine-D (ca
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I. Le tissu adipeux1) Généralité
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(Adenosine triphosphate). Cette pro
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Cette synthèse de novo a lieu dans
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ABFigure 6 : Schéma de la oxydati
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d. Ladipocyte : une cellule sécré
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3) Ladipogenèsea. Les différentes
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. Les facteurs de transcriptionLa d
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Lexpression de C/EBP est quant à e
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adipeux. Les analyses histologiques
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adipocyteFigure 10 : Schéma repré
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II. La cathepsine-D1) Synthèse, ma
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les cath-B et L, en une forme matur
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Il existe deux RM6P : le RM6P/IGFII
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2) Fonctions de la cath-Da. Dans la
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. Dans les pathologiesEn plus de se
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c. Rôles et mécanismes daction da
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carcinome de prostate serait respon
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La cath-D joue donc un rôle import
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Une fois le marquage des peptides e
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Afin de réaliser ce projet, nous a
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III. Le récepteur LRP11) Organisat
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2) Trafic intra-cellulaireComme le
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LRP1αLRP1Membrane associatedprotea
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Tableau 3 : Ligands connus du LRP1(
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I. Etude du rôle de la cathepsine
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Cathepsin-D, a key protease in brea
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IntroductionConsumption of meals ri
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(Fig. 1A, panel a). This differenti
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differentiated adipocyte (Fig. 4B).
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DiscussionOur results demonstrate t
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from normal and peri-al breast adip
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mouse RS9 (sens 5CGGCCCGGGAGCTGTTGA
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agreement of local ethic committee.
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Statistical analysis. Results are e
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Loncarek J, Freiss G, Vignon F and
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Aa3000 *b4000*B8000**cath-D mRNA(ar
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ABcath-D mRNA(ratio RS9)PPARg mRNA(
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A D3 D7 D14D0BaD0 D3 D7 D14D0 D3 D7
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AshLucshcath-DF442A C34 C37 A4 D10c
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AF442-AC34C37A4D10BF442-AC34C37A4D1
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II. Etude du rôle du LRP1 dans les
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2) Article 2:LRP1 receptor controls
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LRP1, Adipogenesis, Obesityrelative
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LRP1, Adipogenesis, ObesityFigure 3
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LRP1, Adipogenesis, ObesityFigure 5
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LRP1, Adipogenesis, ObesitySome ins
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LRP1, Adipogenesis, ObesityLipolysi
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CONCLUSIONLa cathepsine D (cath-D)
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la souris obèses. Enfin, linhibiti
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carcinogénique sont encore mal con
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Ce travail de thèse a étudié, po
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REFERENCESAhima, R. S. (2006). Adip
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implicates them as antigen presenti
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Cataldo, A. M., Barnett, J. L., Ber
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Folkman, J. (2003). Fundamental con
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Hofmann, S. M., Zhou, L., Perez-Til
Page 126 and 127: Langin, D. (2006a). Adipose tissue
Page 128 and 129: Ludwig, T., Ovitt, C. E., Bauer, U.
Page 130 and 131: Nirde, P., Derocq, D., Maynadier, M
Page 132 and 133: Rozanov, D. V., Hahn-Dantona, E., S
Page 134 and 135: Taleb, S., Cancello, R., Clement, K
Page 136 and 137: Xiao, Y., Junfeng, H., Tianhong, L.
Page 138 and 139: F. ANNEXE98
Page 140 and 141: Cathepsin D is a new ligand for ext
Page 142 and 143: INTRODUCTIONLysosomal aspartic prot
Page 144 and 145: pcDNA3.1(+)Myc-tagged LRP1b into pc
Page 146 and 147: (Protein refolding kit, Novagen) fo
Page 148 and 149: anti-mouse-gold (Aurion). Sections
Page 150 and 151: not secrete detectable levels of pr
Page 152 and 153: using cath-D-/- MEF transfected wit
Page 154 and 155: co-culture outgrowth assays with ca
Page 156 and 157: REFERENCES1. Vignon, F., Capony, F.
Page 158 and 159: steps in vivo: proliferation, angio
Page 160 and 161: 28. Laurent-Matha, V., Lucas, A., H
Page 162 and 163: 42. Zurhove, K., Nakajima, C., Herz
Page 164 and 165: Figure 1. Cath-D interacts with the
Page 166 and 167: Figure 2. Cath-D binds to residues
Page 168 and 169: Figure 3. Cath-D interacts with LRP
Page 170 and 171: Figure 5. Silencing LRP1 in cath-D
Page 172 and 173: Figure 1. Cath-D interacts with the
Page 174 and 175: Figure 6. LRP1 is the receptor medi
Page 178: RésuméLaspartyl protéase catheps
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