title: Cathepsin-D, a key protease in breast cancer, is up-regulated in obese mouse and human adipose tissue, and controls adipogenesis.
abstract: The aspartic protease cathepsin-D (cath-D) is overexpressed by human epithelial breast cancer cells and is closely correlated with poor prognosis in breast cancer. The adipocyte is one of the most prominent cell types in the tumor-microenvironment of breast cancer, and clinical studies have shown that obesity increases the incidence of breast cancer. Here, we provide the first evidence that cath-D expression is up-regulated in adipose tissue from obese human beings, as well as in adipocytes from the obese C57BI6/J mouse. Cath-D expression is also increased during human and mouse adipocyte differentiation. We show that cath-D silencing in 3T3-F442A murine preadipocytes leads to lipid-depleted cells after adipogenesis induction, and inhibits of the expression of PPARγ, HSL and aP2 adipocyte differentiation markers. Altogether, our findings demonstrate the key role of cath-D in the control of adipogenesis, and suggest that cath-D may be a novel target in obesity.
authors.affiliation: IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Masson
authors.forename: Christine
authors.initials: C
authors.lastname: Prébois
authors.forename: Danielle
authors.initials: D
authors.lastname: Derocq
authors.forename: Aline
authors.initials: A
authors.lastname: Meulle
authors.forename: Cédric
authors.initials: C
authors.lastname: Dray
authors.forename: Danielle
authors.initials: D
authors.lastname: Daviaud
authors.forename: Didier
authors.initials: D
authors.lastname: Quilliot
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.forename: Catherine
authors.initials: C
authors.lastname: Muller
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Liaudet-Coopman
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D050156:Adipogenesis / Q000235:genetics* / Q000502:physiology; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics; D002402:Cathepsin D / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation
chemical_list: C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma; D010447:Peptide Hydrolases; D002402:Cathepsin D