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

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Statistical analysis. Results are expressed as means ± SEM. Statistical differencesbetween two groups were evaluated using Students t tests. The level of significancewas set at P < 0.05.ACKNOWLEDGEMENTSThis work was supported by the Institut National de la Santé et de la RechercheMédicale, the University of Montpellier I, the Canceropole Grand Sud-Ouest and theInstitut National du Cancer (INCA grants PL2006_035).The authors declare no conflict of interest.CONFLICT OF INTERESTREFERENCESAndarawewa KL, Motrescu ER, Chenard MP, Gansmuller A, Stoll I, Tomasetto C andRio MC. (2005). Cancer Res, 65, 10862-71.Berchem G, Glondu M, Gleizes M, Brouillet JP, Vignon F, Garcia M and Liaudet-Coopman E. (2002). Oncogene, 21, 5951-5.Bouloumie A, Sengenes C, Portolan G, Galitzky J and Lafontan M. (2001). Diabetes,50, 2080-6.Bour S, Daviaud D, Gres S, Lefort C, Prevot D, Zorzano A, Wabitsch M, Saulnier-Blache JS, Valet P and Carpene C. (2007). Biochimie, 89, 916-25.Calle EE and Kaaks R. (2004). Nat Rev Cancer, 4, 579-91.Capony F, Morisset M, Barrett AJ, Capony JP, Broquet P, Vignon F, Chambon M,Louisot P and Rochefort H. (1987). J Cell Biol, 104, 253-62.17
Capony F, Rougeot C, Montcourrier P, Cavailles V, Salazar G and Rochefort H.(1989). Cancer Res, 49, 3904-9.Felbor U, Kessler B, Mothes W, Goebel HH, Ploegh HL, Bronson RT and Olsen BR.(2002). Proc Natl Acad Sci U S A, 99, 7883-8.Ferrandina G, Scambia G, Bardelli F, Benedetti Panici P, Mancuso S and Messori A.(1997). Br J Cancer, 76, 661-6.Foekens JA, Look MP, Bolt-de Vries J, Meijer-van Gelder ME, van Putten WL andKlijn JG. (1999). Br J Cancer, 79, 300-7.Fusek M and Vetvicka V. (1994). Biochem J, 303 ( Pt 3), 775-80.Garcia M, Derocq D, Pujol P and Rochefort H. (1990). Oncogene, 5, 1809-14.Gesta S, Lolmede K, Daviaud D, Berlan M, Bouloumie A, Lafontan M, Valet P andSaulnier-Blache JS. (2003). Horm Metab Res, 35, 158-63.Glondu M, Coopman P, Laurent-Matha V, Garcia M, Rochefort H and Liaudet-Coopman E. (2001). Oncogene, 20, 6920-9.Glondu M, Liaudet-Coopman E, Derocq D, Platet N, Rochefort H and Garcia M.(2002). Oncogene, 21, 5127-34.Hu L, Roth JM, Brooks P, Luty J and Karpatkin S. (2008). Cancer Res, 68, 4666-73.Iyengar P, Espina V, Williams TW, Lin Y, Berry D, Jelicks LA, Lee H, Temple K,Graves R, Pollard J, Chopra N, Russell RG, Sasisekharan R, Trock BJ,Lippman M, Calvert VS, Petricoin EF, 3rd, Liotta L, Dadachova E, Pestell RG,Lisanti MP, Bonaldo P and Scherer PE. (2005). J Clin Invest, 115, 1163-76.Iyengar P and Scherer PE. (2003). Pediatr Diabetes, 4, 32-7.Laurent-Matha V, Maruani-Herrmann S, Prebois C, Beaujouin M, Glondu M, Noel A,Alvarez-Gonzalez ML, Blacher S, Coopman P, Baghdiguian S, Gilles C,18
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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
Page 30 and 31: adipeux. Les analyses histologiques
Page 32 and 33: adipocyteFigure 10 : Schéma repré
Page 34 and 35: II. La cathepsine-D1) Synthèse, ma
Page 36 and 37: les cath-B et L, en une forme matur
Page 38 and 39: Il existe deux RM6P : le RM6P/IGFII
Page 40 and 41: 2) Fonctions de la cath-Da. Dans la
Page 42 and 43: . Dans les pathologiesEn plus de se
Page 44 and 45: c. Rôles et mécanismes daction da
Page 46 and 47: carcinome de prostate serait respon
Page 48 and 49: La cath-D joue donc un rôle import
Page 50 and 51: Une fois le marquage des peptides e
Page 52 and 53: Afin de réaliser ce projet, nous a
Page 54 and 55: III. Le récepteur LRP11) Organisat
Page 56 and 57: 2) Trafic intra-cellulaireComme le
Page 58 and 59: LRP1αLRP1Membrane associatedprotea
Page 60 and 61: Tableau 3 : Ligands connus du LRP1(
Page 62 and 63: I. Etude du rôle de la cathepsine
Page 64 and 65: Cathepsin-D, a key protease in brea
Page 66 and 67: IntroductionConsumption of meals ri
Page 68 and 69: (Fig. 1A, panel a). This differenti
Page 70 and 71: differentiated adipocyte (Fig. 4B).
Page 72 and 73: DiscussionOur results demonstrate t
Page 74 and 75: from normal and peri-al breast adip
Page 76 and 77: mouse RS9 (sens 5CGGCCCGGGAGCTGTTGA
Page 78 and 79: agreement of local ethic committee.
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
Page 92 and 93: AF442-AC34C37A4D10BF442-AC34C37A4D1
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)
Page 110 and 111: la souris obèses. Enfin, linhibiti
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 126 and 127: Langin, D. (2006a). Adipose tissue
Page 128 and 129: Ludwig, T., Ovitt, C. E., Bauer, U.
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Nirde, P., Derocq, D., Maynadier, M
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Rozanov, D. V., Hahn-Dantona, E., S
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Taleb, S., Cancello, R., Clement, K
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Xiao, Y., Junfeng, H., Tianhong, L.
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F. ANNEXE98
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Cathepsin D is a new ligand for ext
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INTRODUCTIONLysosomal aspartic prot
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pcDNA3.1(+)Myc-tagged LRP1b into pc
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(Protein refolding kit, Novagen) fo
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anti-mouse-gold (Aurion). Sections
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not secrete detectable levels of pr
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using cath-D-/- MEF transfected wit
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co-culture outgrowth assays with ca
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REFERENCES1. Vignon, F., Capony, F.
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steps in vivo: proliferation, angio
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28. Laurent-Matha, V., Lucas, A., H
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42. Zurhove, K., Nakajima, C., Herz
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Figure 1. Cath-D interacts with the
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Figure 2. Cath-D binds to residues
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Figure 3. Cath-D interacts with LRP
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Figure 5. Silencing LRP1 in cath-D
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Figure 1. Cath-D interacts with the
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Figure 6. LRP1 is the receptor medi
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Beaujouin, Figure Sup. 2cath-D-/-ME
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RésuméLaspartyl protéase catheps
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