Dietary soy effects on early rat mammary gland development

The linkage between nutrition and cancer prevention is an intriguing concept that is gaining widespread support based on epidemiological and animal studies. Multiple mechanisms likely underlie dietary protection against cancer, with effects influenced by target tissue response, cell-cell interactions and developmental context. Given the negative correlation between breast cancer incidence and intake of soy foods by Asian women, and the increasing consumption of soy protein-based formula by infants in the Western world, we have studied soy protein isolate (SPI) used in most infant formula as a paradigm to evaluate diet as a risk factor in a rodent model of mammary cancer. We previously demonstrated that lifetime exposure to dietary SPI reduced the incidence of N-methyl-N-nitrosourea-induced mammary tumors in young adult rats relative to those fed the control diet Casein (CAS). This protection was associated with increased tumor suppressor PTEN and decreased Wnt signaling component expression in mammary epithelial cells at postnatal day (PND) 50 prior to carcinogen insult. To identify early events contributing to mammary tumor suppression by diet, we used Affymetrix RAE230A GeneChips containing 14280 probe sets and the GeneSpring Robust Multi-array program to analyze genomic profiles of mammary glands of prepubertal (PND21) rats lifetime exposed to SPI or CAS.营养与癌症预防之间的关联是一个引人入胜的概念，基于流行病学与动物研究，该观点正获得越来越广泛的认可。饮食对癌症的防护作用可能由多种机制介导，其效果受靶组织应答、细胞间相互作用以及发育背景的调控。鉴于亚洲女性乳腺癌发病率与大豆食品摄入量呈负相关，且西方世界婴幼儿食用大豆蛋白基配方食品的比例日益攀升，本研究以多数婴儿配方食品中使用的大豆分离蛋白（soy protein isolate, SPI）为研究模型，在乳腺癌啮齿类动物模型中评估饮食作为风险因素的效应。我们此前已证实，与喂食对照饮食酪蛋白（Casein, CAS）的大鼠相比，终生摄入膳食SPI可降低年轻成年大鼠中N-甲基-N-亚硝基脲诱导的乳腺肿瘤发病率。该保护效应与致癌物暴露前的出生后第50天（postnatal day, PND）乳腺上皮细胞中，肿瘤抑制因子PTEN表达上调、Wnt信号通路组分表达下调密切相关。为明确饮食介导乳腺肿瘤抑制的早期事件，我们使用搭载14280个探针组的Affymetrix RAE230A基因芯片，结合GeneSpring稳健多阵列分析程序，对终生暴露于SPI或CAS的青春期前（出生后第21天，PND21）大鼠的乳腺组织基因组谱进行了分析。