Fish oil alters tamoxifen-modulated expression of genes related to differentiation, proliferation, metastasis, and immune response in rat mammary tumors

Herein, we evidence that tamoxifen treatment modifies gene expression of mammary tumors depending upon the type of dietary fat fed to the animals. Rats initiated with MNU and treated with tam were fed a diet rich in corn oil (CO) or fish oil (FO). After 8 weeks, tumors of the same histological type (cribriform) were collected and comprehensive analysis of messenger RNA expression was performed. The mRNA expression of genes such as SerpinB10, Wisp2 and Apod in tumors from FO-treated rats is indicative of highly differentiated tumors. Decreased expression of H19 and Igf2 mRNA in tam-treated groups, and Thrsp and Wnt5b mRNA in FOtam group may be related to tumor growth impairment and lower metastatic capacity. Increased Irf7, RT1-CE3, RT1-CE16 transcript levels in FO-treated animals suggests an improved immune response against tumors (Th1 pattern) whereas decreased mRNA of Fcer1a, Hdc, Ms4a2, Slp1, Mcpt1 and Mcpt2 may indicate a shift of the immune response towards Th2 pattern.本研究证实，他莫昔芬（tamoxifen）对乳腺肿瘤基因表达的调控作用，取决于实验动物所摄入的膳食脂肪类型。本研究中，经N-甲基-N-亚硝基脲（MNU）诱导并接受他莫昔芬（tam）处理的大鼠，被喂食富含玉米油（CO）或鱼油（FO）的饲料。饲养8周后，收集相同组织学类型（筛状型）的肿瘤样本，并对其信使RNA（mRNA）表达进行全面分析。在喂食鱼油的大鼠肿瘤中，SerpinB10、Wisp2及Apod等基因的mRNA表达水平，提示该类肿瘤为高分化肿瘤。他莫昔芬处理组中H19与Igf2的mRNA表达下调，而鱼油联合他莫昔芬组中Thrsp及Wnt5b的mRNA表达下调，这可能与肿瘤生长受抑及转移能力降低相关。喂食鱼油的大鼠体内Irf7、RT1-CE3及RT1-CE16的转录本水平升高，提示其抗肿瘤免疫应答呈现Th1型极化特征；而Fcer1a、Hdc、Ms4a2、Slp1、Mcpt1及Mcpt2的mRNA表达下调，则可能表明其免疫应答向Th2型偏移。