IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France.
PLoS One. 2011 Feb 2;6(2):e16452. doi: 10.1371/journal.pone.0016452.
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.
天冬氨酸蛋白酶组织蛋白酶 D (cath-D) 在人类上皮性乳腺癌细胞中过度表达，与乳腺癌的不良预后密切相关。脂肪细胞是乳腺癌肿瘤微环境中最突出的细胞类型之一，临床研究表明肥胖会增加乳腺癌的发病率。在这里，我们首次提供证据表明，肥胖人群的脂肪组织和肥胖 C57BI6/J 小鼠的脂肪细胞中 cath-D 的表达上调。在人和小鼠脂肪细胞分化过程中，cath-D 的表达也增加。我们表明，在 3T3-F442A 鼠前脂肪细胞中沉默 cath-D 会导致脂肪生成诱导后细胞内脂质耗竭，并抑制 PPARγ、HSL 和 aP2 脂肪细胞分化标志物的表达。总之，我们的研究结果表明 cath-D 在控制脂肪生成中起着关键作用，并表明 cath-D 可能是肥胖症的一个新靶点。
