Genistein chemoprevention: Timing and mechanisms of action in murine mammary and prostate
Genistein chemoprevention: Timing and mechanisms of action in murine mammary and prostate
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DOI：
10.1093/jn/132.3.552s
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发表时间：
2002-03-01
影响因子：
4.2
通讯作者：
Elgavish, A
中科院分区：
文献类型：
--
作者：
Lamartiniere, CA;Cotroneo, MS;Elgavish, A
我们在动物模型中研究了大豆的主要成分染料木黄酮预防乳腺癌和前列腺癌的潜力。对于乳腺癌研究，给Sprague-Dawley大鼠喂食AlN-76 A饮食+/-250 mg染料木黄酮/kg饮食。在产后第50天用二甲基苯并[a]蒽灌胃诱发乳腺肿瘤。乳腺癌的化学预防后，青春期前和青春期前和成人染料木黄酮联合治疗，但不是在产前或成人的治疗，表明暴露于染料木黄酮的时机是重要的乳腺癌的化学预防。发现细胞作用机制是乳腺和细胞分化，如整体包埋分析和β-酪蛋白表达所示。表皮生长因子受体在乳腺末端芽中的表达具有印迹效应。对于前列腺癌研究，我们使用了两种模型。第一个是化学（N-甲基亚硝基脲）诱导的前列腺癌大鼠模型。饮食中的染料木黄酮以剂量依赖的方式抑制浸润性腺癌的发展。第二个模型是转基因小鼠模型，导致自发发展的前列腺腺癌肿瘤。饮食中的染料木黄酮以剂量依赖性方式降低低分化前列腺癌的发生率，并下调雄激素受体、雌激素受体-α、孕激素受体、表皮生长因子受体、胰岛素样生长因子-I和细胞外信号调节激酶-1，但不下调雌激素受体-β和转化生长因子-α mRNA的表达。我们的结论是，膳食染料木素通过调节特定的性类固醇受体和生长因子信号通路来预防乳腺癌和前列腺癌。
We investigated the potential of genistein, the primary isoflavone of soy, to protect against breast and prostate cancers in animal models. For mammary cancer studies, Sprague-Dawley rats were fed AlN-76A diet +/- 250 mg genistein/kg diet. Dimethylbenz[a]anthracene was administered by gavage at d 50 postpartum to induce mammary tumors. Mammary cancer chemoprevention was demonstrated after prepubertal and combined prepubertal and adult genistein treatments but not after prenatal- or adult-only treatments, demonstrating that the timing of exposure to genistein is important for mammary cancer chemoprevention. The cellular mechanism of action was found to be mammary gland and cell differentiation, as shown by whole-mount analysis and beta-casein expression. An imprinting effect was shown for epidermal growth factor receptor expression in mammary terminal end buds. For prostate cancer studies, we used two models. The first was a chemically (N-methylnitrosourea) induced prostate cancer rat model. Genistein in the diet inhibited the development of invasive adenocarcinomas in a dose-dependent manner. The second model was a transgenic mouse model that resulted in spontaneously developing adenocarcinoma tumor of the prostate. Genistein in the diet reduced the incidence of poorly differentiated prostatic adenocarcinomas in a dose-dependent manner and down-regulated androgen receptor, estrogen receptor-alpha, progesterone receptor, epidermal growth factor receptor, insulin-like growth factor-I, and extracellular signal-regulated kinase-1 but not estrogen receptor-beta and transforming growth factor-alpha mRNA expressions. We conclude that dietary genistein protects against mammary and prostate cancers by regulating specific sex steroid receptors and growth factor signaling pathways.