Langin, D. (2006a). Adipose tissue lipolysis as a m<strong>et</strong>abolic pathway to <strong>de</strong>finepharmacological strategies against obesity and the m<strong>et</strong>abolic syndrome. Pharmacol Res 53,482-491.Langin, D. (2006b). Control of fatty acid and glycerol release in adipose tissue lipolysis. C RBiol 329, 598-607; discussion 653-595.Large, V., and Arner, P. (1998). Regu<strong>la</strong>tion of lipolysis in humans. Pathophysiologicalmo<strong>du</strong><strong>la</strong>tion in obesity, diab<strong>et</strong>es, and hyperlipidaemia. Diab<strong>et</strong>es M<strong>et</strong>ab 24, 409-418.Large, V., Peroni, O., L<strong>et</strong>exier, D., Ray, H., and Beylot, M. (2004). M<strong>et</strong>abolism of lipids inhuman white adipocyte. Diab<strong>et</strong>es M<strong>et</strong>ab 30, 294-309.Laurent-Matha, V., Derocq, D., Prebois, C., Katunuma, N., and Liaud<strong>et</strong>-Coopman, E. (2006).Processing of human cathepsin D is in<strong>de</strong>pen<strong>de</strong>nt of its catalytic function and auto-activation:involvement of cathepsins L and B. J Biochem 139, 363-371.Laurent-Matha, V., Farnoud, M. R., Lucas, A., Rougeot, C., Garcia, M., and Rochefort, H.(1998). Endocytosis of pro-cathepsin D into breast cancer cells is mostly in<strong>de</strong>pen<strong>de</strong>nt ofmannose-6-phosphate receptors. J Cell Sci 111 ( Pt 17), 2539-2549.Laurent-Matha, V., Lucas, A., Huttler, S., Sandhoff, K., Garcia, M., and Rochefort, H. (2002).Procathepsin D interacts with prosaposin in cancer cells but its internalization is not mediatedby LDL receptor-re<strong>la</strong>ted protein. Exp Cell Res 277, 210-219.Laurent-Matha, V., Maruani-Herrmann, S., Prebois, C., Beaujouin, M., Glon<strong>du</strong>, M., Noel, A.,Alvarez-Gonzalez, M. L., B<strong>la</strong>cher, S., Coopman, P., Baghdiguian, S., <strong>et</strong> al. (2005).Catalytically inactive human cathepsin D triggers fibrob<strong>la</strong>st invasive growth. J Cell Biol 168,489-499.Lee, A. Y., Gulnik, S. V., and Erickson, J. W. (1998). Conformational switching in an asparticproteinase. Nat Struct Biol 5, 866-871.Lee, D., Walsh, J. D., Mikhailenko, I., Yu, P., Migliorini, M., Wu, Y., Krueger, S., Curtis, J.E., Harris, B., Lock<strong>et</strong>t, S., <strong>et</strong> al. (2006). RAP uses a histidine switch to regu<strong>la</strong>te its interactionwith LRP in the ER and Golgi. Mol Cell 22, 423-430.Lefterova, M. I., and Lazar, M. A. (2009). New <strong>de</strong>velopments in adipogenesis. TrendsEndocrinol M<strong>et</strong>ab 20, 107-114.Lefterova, M. I., Zhang, Y., Steger, D. J., Schupp, M., Schug, J., Cristancho, A., Feng, D.,Zhuo, D., Stoeckert, C. J., Jr., Liu, X. S., and Lazar, M. A. (2008). PPARgamma and C/EBPfactors orchestrate adipocyte biology via adjacent binding on a genome-wi<strong>de</strong> scale. GenesDev 22, 2941-2952.86
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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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- Page 80 and 81: Statistical analysis. Results are e
- Page 82 and 83: Loncarek J, Freiss G, Vignon F and
- Page 84 and 85: Aa3000 *b4000*B8000**cath-D mRNA(ar
- Page 86 and 87: ABcath-D mRNA(ratio RS9)PPARg mRNA(
- Page 88 and 89: A D3 D7 D14D0BaD0 D3 D7 D14D0 D3 D7
- Page 90 and 91: AshLucshcath-DF442A C34 C37 A4 D10c
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- Page 94 and 95: II. Etude du rôle du LRP1 dans les
- Page 96 and 97: 2) Article 2:LRP1 receptor controls
- Page 98 and 99: LRP1, Adipogenesis, Obesityrelative
- Page 100 and 101: LRP1, Adipogenesis, ObesityFigure 3
- Page 102 and 103: LRP1, Adipogenesis, ObesityFigure 5
- Page 104 and 105: LRP1, Adipogenesis, ObesitySome ins
- Page 106 and 107: LRP1, Adipogenesis, ObesityLipolysi
- Page 108 and 109: CONCLUSIONLa cathepsine D (cath-D)
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- Page 112 and 113: carcinogénique sont encore mal con
- Page 114 and 115: Ce travail de thèse a étudié, po
- Page 116 and 117: REFERENCESAhima, R. S. (2006). Adip
- Page 118 and 119: implicates them as antigen presenti
- Page 120 and 121: Cataldo, A. M., Barnett, J. L., Ber
- Page 122 and 123: Folkman, J. (2003). Fundamental con
- Page 124 and 125: Hofmann, S. M., Zhou, L., Perez-Til
- 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
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- 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
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- Page 172 and 173: Figure 1. Cath-D interacts with the
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Beaujouin, Figure Sup. 2cath-D-/-ME
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RésuméLaspartyl protéase catheps