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: Olivier Masson, Christine Prébois, Danielle Derocq, Aline Meulle, Cédric Dray, Danielle Daviaud, Didier Quilliot, Philippe Valet, Catherine Muller, Emmanuelle Liaudet-Coopman
• Journal: PloS one (PLoS One) Vol. 6 Issue 2 Pg. e16452 (Feb 02 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 21311773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fabp4 protein, mouse
• Fatty Acid-Binding Proteins
• PPAR gamma
• Peptide Hydrolases
• Cathepsin D

Topics

• 3T3 Cells
• Adipocytes (metabolism, pathology)
• Adipogenesis (genetics, physiology)
• Adipose Tissue (metabolism, pathology)
• Animals
• Breast Neoplasms (enzymology, genetics)
• Carcinoma (enzymology, genetics)
• Cathepsin D (genetics, metabolism, physiology)
• Cells, Cultured
• Fatty Acid-Binding Proteins (genetics, metabolism)
• Female
• Gene Expression Regulation, Enzymologic (physiology)
• Humans
• Mice
• Mice, Inbred C57BL
• Obesity (enzymology, genetics, pathology)
• PPAR gamma (genetics, metabolism)
• Peptide Hydrolases (genetics, metabolism, physiology)
• Up-Regulation