Motta Massimiliano, Accornero Paolo, Taulli Riccardo, Bernabei Paola, Desrivières Sylvane, Baratta Mario
Department of Veterinary Morphophysiology, University of Torino, Via Leonardo da Vinci 44, 10095 Grugliasco, TO, Italy.
Mol Cell Endocrinol. 2007 Jan 15;263(1-2):149-55. doi: 10.1016/j.mce.2006.09.010. Epub 2006 Oct 30.
Leptin is produced in the mammary gland by the fat tissue or by the mammary epithelium. The aim of this study was to investigate the role of leptin on mammary epithelial cell differentiation and cell viability. This study was conducted using the mouse mammary epithelial cell line HC11. We show that leptin, synergizes with prolactin to increase beta-casein gene expression during mammary epithelial cell differentiation. This was correlated with increased phosphorylation of the signal transducer and activator of transcription 3 (STAT-3). Inactivating the function of STAT-3 by expression of a short hairpin RNA demonstrated that the effect of leptin on beta-casein expression is mediated by STAT-3. Secondly, cells in which STAT-3 had been inactivated showed increased cell viability compared to controls and were resistant to the negative effect mediated by leptin. Further, leptin triggers apoptosis in mammary epithelial cells cultivated in non-differentiating conditions. Taken together, these results suggest that leptin, by activating STAT-3, may act as a paracrine factor modulating mammary epithelial cell function.
瘦素由脂肪组织或乳腺上皮细胞在乳腺中产生。本研究的目的是探讨瘦素在乳腺上皮细胞分化和细胞活力中的作用。本研究使用小鼠乳腺上皮细胞系HC11进行。我们发现，在乳腺上皮细胞分化过程中，瘦素与催乳素协同作用，增加β-酪蛋白基因的表达。这与信号转导子和转录激活子3（STAT-3）磷酸化增加相关。通过表达短发夹RNA使STAT-3功能失活表明，瘦素对β-酪蛋白表达的影响是由STAT-3介导的。其次，与对照相比，STAT-3失活的细胞显示出细胞活力增加，并且对瘦素介导的负面影响具有抗性。此外，瘦素在非分化条件下培养的乳腺上皮细胞中引发凋亡。综上所述，这些结果表明，瘦素通过激活STAT-3，可能作为一种旁分泌因子调节乳腺上皮细胞功能。
