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

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Aa3000 *b4000*B8000**cath-D mRNA(arbitrary unit)20001000300020001000cath-D mRNA(arbitrary unit)6000400020000normalVATobeseVAT0normalSATobeseSAT0NDHFDFigure 1Figure 1. Cath-D expression is up-regulated in human and mouse obese adiposetissues(A) Cath-D expression in adipose tissue from lean and obese human. Cath-D mRNAlevel was quantified in human intra-abdominal visceral adipose tissue samples (VAT)(panel a) and in human subcutaneous adipose tissue samples (SAT) (panel b) obtainedfrom 27 morbide grade III obese patients (44.5+/-1.8 year old, BMI: 47.6 +/- 1.3 kg/m2)before a bariatric surgery and from 9 control patients undergoing abdominal lipectomy forplastic surgery (42.7 +/- 4.5 year old, BMI: 23.1 +/- 3.3 kg/m2). Results are means +/-SEM, *P
3T3-F442A3T3-L1Co D7 Co D7NIH-3T3HMFMCF-7cath-D52K -48K -34K -a-tubulinFigure 2Figure 2. Cath-D expression in pre-adipocytes, adipocytes, fibroblasts and breastepithelial cancer cellsCath-D expression was analysed by immunoblotting in confluent preadipocytes (Co) andadipocytes differentiated for 7 days (D7) in NIH-3T3F442A and NIH-3T3-L1 cell lines, inNIH-3T3 mouse fibroblasts, HMF human breast fibroblasts, and MCF-7 human epithelialbreast cancer cells . a-tubulin served as a loading control.
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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
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 80 and 81: Statistical analysis. Results are e
Page 82 and 83: Loncarek J, Freiss G, Vignon F and
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.
Page 130 and 131: Nirde, P., Derocq, D., Maynadier, M
Page 132 and 133: 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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