The inhibition of early stages of HER-2/neu-mediated mammary carcinogenesis by dietary n-3 PUFAs.
The inhibition of early stages of HER-2/neu-mediated mammary carcinogenesis by dietary n-3 PUFAs.
复制标题
膳食 n-3 PUFA 抑制 HER-2/neu 介导的早期乳腺癌发生。
DOI：
10.1002/mnfr.201200445
复制
发表时间：
2013
影响因子：
5.2
通讯作者：
Clinton,StevenK
中科院分区：
文献类型：
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作者：
Yee,LisaD;Agarwal,Deepak;Rosol,ThomasJ;Lehman,Amy;Tian,Min;Hatton,Jennifer;Heestand,Jessica;Belury,MarthaA;Clinton,StevenK
范围我们之前证明，终身喂养富含 inn-3 脂肪酸（例如二十二碳六烯酸（DHA）和二十碳五烯酸（EPA））的饮食可显着抑制小鼠 HER-2/neu 介导的乳腺肿瘤发生。令人感兴趣的是膳食 n-3 脂肪酸是否在乳腺癌发生的早期阶段发挥作用。方法和结果七周大的雌性 MMTV-HER-2/neu 转基因小鼠被随机分配到基于 AIN 的半纯化饮食中，其中含有 25% 能量的鱼油或玉米油。在 25、30 和 35 周时对小鼠进行评估，分析乳腺的非典型导管增生（苏木精和伊红）、细胞增殖（Ki67 免疫染色）以及脂肪酸合酶和环氧合酶 2 基因表达（qRT-PCR）。通过GC对组织脂肪酸谱进行定量。喂食鱼油的小鼠的异型性等级显着降低（p = 0.002）。喂食鱼油的小鼠乳腺中的乳腺上皮细胞的 Ki67 表达百分比也降低了八倍。与富含玉米油的饮食相比，喂鱼的小鼠乳腺脂肪垫中的 COX-2 表达显着降低。 结论 相对于玉米油饮食，膳食鱼油可抑制 HER-2/neu 介导的乳腺癌发生早期阶段的非典型导管增生。这种组织学变化与乳腺上皮细胞增殖的抑制和乳腺组织中 COX-2 表达的减少有关。
ScopeWe previously demonstrated that lifelong feeding of diets enriched inn‐3 fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) significantly inhibits HER‐2/neu‐mediated mammary tumorigenesis in mice. Of interest is whether dietaryn‐3 fatty acids exert effects at early stages of mammary carcinogenesis.Methods and resultsSeven‐week‐old female MMTV‐HER‐2/neu transgenic mice were randomized to AIN‐based semipurified diets containing either fish or corn oil at 25% energy. Mice were evaluated at 25, 30, and 35 weeks with analysis of mammary glands for atypical ductal hyperplasia (hematoxylin and eosin), cell proliferation (Ki67 immunostaining), and fatty acid synthase and cyclooxygenase‐2 gene expression (qRT‐PCR). Tissue fatty acid profiles were quantitated by GC. Atypia grade decreased significantly in mice fed fish oil (p= 0.002). Mammary epithelial cells in mammary glands from mice fed fish oil also had an eightfold lower percentage of Ki67 expression. COX‐2 expression in mammary fat‐pads significantly decreased in mice fed fish versus corn oil enriched diets.ConclusionDietary fish oil inhibits atypical ductal hyperplasia at early stages of HER‐2/neu‐mediated mammary carcinogenesis relative to corn oil diets. This histologic change is associated with suppression of mammary epithelial cell proliferation and decreased COX‐2 expression in mammary tissue.