Section of Medical Oncology, Department of Surgical and Oncological Sciences, University of Palermo, Palermo, Italy.
J Cell Physiol. 2013 Jun;228(6):1368-74. doi: 10.1002/jcp.24295.
The obesity hormone leptin has been implicated in breast cancer development. Breast cancer cells express the leptin receptor and are able to synthesize leptin in response to obesity-related stimuli. Furthermore, leptin is a positive regulator of vascular endothelial growth factor (VEGF) and high levels of both proteins are associated with worse prognosis in breast cancer patients. Peroxisome proliferator-activated receptor γ (PPARγ) ligands are therapeutic agents used in patient with Type 2 diabetes and obesity which have recently been studied for their potential anti-tumor effect. Here, we studied if these compounds, ciglitazone and GW1929, can affect the expression of leptin and VEGF in breast cancer cells. In MDA-MB-231 and MCF-7 breast cancer cells, treatment with submolar concentrations of ciglitazone and GW1929 elevated the expression of leptin and VEGF mRNA and protein, and increased cell viability and migration. These effects coincided with increased recruitment of PPARγ to the proximal leptin promoter and decreased association of a transcriptional factor Sp1 with this DNA region.
肥胖激素瘦素已被牵连到乳腺癌的发展中。乳腺癌细胞表达瘦素受体，并能够响应肥胖相关刺激合成瘦素。此外，瘦素是血管内皮生长因子 (VEGF) 的正调节剂，并且两种蛋白质的高水平都与乳腺癌患者的预后不良相关。过氧化物酶体增殖物激活受体 γ (PPARγ) 配体是用于治疗 2 型糖尿病和肥胖症患者的治疗药物，最近已经研究了它们的潜在抗肿瘤作用。在这里，我们研究了这些化合物，西格列汀和 GW1929 是否可以影响乳腺癌细胞中瘦素和 VEGF 的表达。在 MDA-MB-231 和 MCF-7 乳腺癌细胞中，亚摩尔浓度的西格列汀和 GW1929 处理可上调瘦素和 VEGF mRNA 和蛋白的表达，并增加细胞活力和迁移。这些作用与 PPARγ 募集到瘦素启动子的近端以及转录因子 Sp1 与该 DNA 区域的结合减少有关。
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