Solanas Montserrat, Moral Raquel, Garcia Gemma, Grau Laura, Vela Elena, Escrich Raquel, Costa Irmgard, Escrich Eduard
Department of Cell Biology, Physiology and Immunology, Medical Physiology Unit, Medicine School, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
Eur J Cancer Prev. 2009 Apr;18(2):153-61. doi: 10.1097/CEJ.0b013e3283136308.
Dietary lipids have a role in the aetiology of breast cancer. We have reported earlier that a high corn oil diet downregulates H19 and vitamin D3 upregulated protein 1 (VDUP1) messenger RNA (mRNA) expression in rat dimethylbenz (alpha) anthracene-induced mammary adenocarcinomas in comparison with the control low-fat diet, this effect being associated with a higher degree of tumour malignancy. This result was compatible with the stimulating effect of this diet. In this study we have investigated the influence of a high extra virgin olive diet on H19 and VDUP1 mRNA and/or protein expression. We have shown earlier that this high-fat diet confers to the tumours a more benign phenotype in accordance with its potential protective effect on mammary cancer. We have also analysed the effects on the mRNA and protein expression of insulin-like growth factor-2 , in close relation with H19, and the expression and activity of the thioredoxin protein, negatively regulated by VDUP1. mRNA and protein expression were analysed by chemiluminescent northern blot and western blot, respectively. Thioredoxin activity was determined by the insulin-reducing assay. The results showed that the high olive oil diet does not change the tumour expression of H19 and VDUP1. Moreover, tumours from the animals fed this diet displayed higher levels of the insulin-like growth factor-2 mRNAs, which are related to a higher rate of degradation or a lower traducibility. Finally, tumour expression and activity levels of thioredoxin-1 protein did not change irrespective of the diet. These results suggest that the differential effects of high olive oil and high corn oil diets on mammary cancer are exerted by means of a different, specific influence on gene expression.
膳食脂质在乳腺癌的病因学中发挥作用。我们之前报道过,与对照低脂饮食相比,高玉米油饮食会下调大鼠二甲基苯并(α)蒽诱导的乳腺腺癌中H19和维生素D3上调蛋白1(VDUP1)信使核糖核酸(mRNA)的表达,这种效应与更高程度的肿瘤恶性程度相关。这一结果与这种饮食的刺激作用相符。在本研究中,我们调查了高特级初榨橄榄油饮食对H19和VDUP1 mRNA及/或蛋白表达的影响。我们之前已经表明,这种高脂肪饮食赋予肿瘤更良性的表型,这与其对乳腺癌的潜在保护作用一致。我们还分析了与H19密切相关的胰岛素样生长因子-2的mRNA和蛋白表达的影响,以及受VDUP1负调控的硫氧还蛋白的表达和活性。分别通过化学发光Northern印迹和Western印迹分析mRNA和蛋白表达。通过胰岛素还原测定法测定硫氧还蛋白活性。结果表明,高橄榄油饮食不会改变肿瘤中H19和VDUP1的表达。此外,喂食这种饮食的动物的肿瘤显示出更高水平的胰岛素样生长因子-2 mRNA,这与更高的降解率或更低的翻译率有关。最后,无论饮食如何,硫氧还蛋白-1蛋白的肿瘤表达和活性水平均未改变。这些结果表明,高橄榄油饮食和高玉米油饮食对乳腺癌的不同影响是通过对基因表达的不同、特定影响来实现的。