Dietary olive oil and corn oil differentially affect experimental breast cancer through distinct modulation of the p21Ras signaling and the proliferation-apoptosis balance.
Dietary olive oil and corn oil differentially affect experimental breast cancer through distinct modulation of the p21Ras signaling and the proliferation-apoptosis balance.
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DOI：
10.1093/carcin/bgp243
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发表时间：
2010-05
期刊：
影响因子：
4.7
通讯作者：
M. Solanas;Laura Grau;R. Moral;E. Vela;Raquel Escrich;E. Escrich
中科院分区：
文献类型：
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作者：
M. Solanas;Laura Grau;R. Moral;E. Vela;Raquel Escrich;E. Escrich
特级初榨橄榄油（EVOO）已被假设有化学预防乳腺癌的影响，不像高玉米油（HCO）的饮食，刺激it. We研究了这些差异的调节作用对实验性乳腺癌的机制。在7，1/2-二甲基苯并（a）蒽腺癌大鼠饲养高EVOO，HCO和对照饮食（n = 20每组），我们分析了表达和活性的Erb B受体，p21 Ras和其细胞外信号调节激酶（ERK）1/2，Akt和RalA/B效应通过免疫印迹分析。我们通过Southern印迹、错配扩增突变分析和测序检测Ha-ras 1突变状态，并通过实时聚合酶链反应检测3-羟基-3-甲基戊二酰辅酶A还原酶和角鲨烯合成酶mRNA表达。我们通过Caspase-3分析和末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记法分析了肿瘤有丝分裂指数、增殖细胞核抗原（PCNA）水平和细胞凋亡。最后，我们测量了8-氧代-2 '-脱氧鸟苷水平。使用非参数统计。与对照组相比，EVOO饮食降低了Ras活化，下调了Ras/磷脂酰肌醇3-激酶/Akt通路，上调了Raf/Erk通路。相比之下，HCO饮食没有改变Ras活性，而是增强了Raf/Erk途径。与HCO饮食相比，EVOO饮食降低了切割的ErbB 4水平，增加了细胞凋亡并降低了与DNA损伤相关的单泛素化PCNA水平。喂食EVOO饮食的大鼠的肿瘤显示出更良性的表型，而喂食HCO饮食的大鼠的肿瘤在生物学上更具侵略性。总之，高EVOO和玉米油饮食通过Ras信号通路的不同组合、不同的增殖-凋亡平衡和可能不同的DNA损伤水平对乳腺癌发挥其调节作用。
Extra-virgin olive oil (EVOO) has been hypothesized to have chemopreventive effects on breast cancer, unlike high corn oil (HCO) diets that stimulate it. We have investigated mechanisms of these differential modulatory actions on experimental mammary cancer. In 7,12-dimethylbenz(a)anthracene adenocarcinomas of rats fed a high EVOO, HCO and control diets (n = 20 for each group), we have analyzed the expression and activity of ErbB receptors, p21Ras and its extracellular signal-regulated kinase (ERK) 1/2, Akt and RalA/B effectors by immunoblotting analyses. We explored the Ha-ras1 mutation status by Southern blot, mismatch amplification mutation assay and sequencing, and the 3-hydroxy-3-methylglutaryl-coenzyme A reductase and squalene synthase messenger RNA expression by real-time polymerase chain reaction. We analyzed the tumor mitotic index, proliferating cell nuclear antigen (PCNA) levels, and apoptosis through Caspase-3 analysis and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assays. Finally, we measured the 8-oxo-2'-deoxyguanosine levels. Non-parametrical statistics were used. The EVOO diet decreased Ras activation, downregulated the Ras/phosphatidyl inositol 3-kinase/Akt pathway and upregulated the Raf/Erk pathway, compared with the control. In contrast, the HCO diet did not modify Ras activity but rather enhanced the Raf/Erk pathway. The EVOO diet decreased the cleaved ErbB4 levels, compared with the HCO diet, increased apoptosis and diminished the mono-ubiquitylated PCNA levels, which is related to DNA damage. Tumors from rats fed the EVOO diet displayed a more benign phenotype, whereas those from rats fed the HCO diet were biologically more aggressive. In conclusion, high EVOO and corn oil diets exert their modulatory effects on breast cancer through a different combination of Ras signaling pathways, a different proliferation-apoptosis balance and probably distinct levels of DNA damage.