Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis.
Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis.
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DOI：
10.1158/1940-6207.capr-14-0182
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发表时间：
2014-12
期刊：
影响因子：
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通讯作者：
Clinton SK
中科院分区：
文献类型：
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作者：
Wan L;Tan HL;Thomas-Ahner JM;Pearl DK;Erdman JW Jr;Moran NE;Clinton SK
食用含有类胡萝卜素番茄红素的番茄产品与前列腺癌风险降低有关。为了确定与睾丸激素驱动的早期前列腺癌相关的基因表达模式，饮食中的西红柿和番茄红素影响了这一基因表达模式，野生型(WT)和转基因小鼠前列腺癌(TRAMP)在4-10周龄时被喂以对照或含番茄或番茄红素的日粮。8周龄的小鼠接受假手术、去势或去势，然后补充睾酮(去势后1wk开始2.5 mg/kg/d)。10周龄完整的TRAMP小鼠表现出早期的多灶性前列腺上皮内瘤变(PIN)。在Quantity NanoString®检测到的200个前列腺癌相关基因中，189个是可检测到的，164个基因因基因类型而有显著差异，179个基因与睾酮状态有关，30个基因与饮食类型有关(P<；0.05)。在TRAMP中，Birc5、Mki67、Aurkb、Ccnb2、FOXM1和Ccne2的表达高于WT，并且在去势后表达减弱。同时，与完整和睾丸激素复制的流浪鼠相比，去势减少了Ki67阳性染色(P<；0.0001)。参与雄激素代谢/信号通路的基因的表达被番茄红素(Srd5a1)和番茄(Srd5a2、PXN和Srebf1)降低。此外，饲喂番茄显著降低了干细胞特征相关基因Aldh1a和Ly6a的表达，而饲喂番茄红素显著降低了神经内分泌分化相关基因Ngfr和SYP的表达。总而言之，这些研究展示了与前列腺癌早期阶段相关的睾酮调节基因的概况，这些基因是饮食番茄成分的潜在机制靶点。未来对雄激素信号/代谢、干细胞特征和神经内分泌分化途径的研究可能会阐明饮食中番茄和番茄红素影响前列腺癌风险的机制。
Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4-10 wk-of-age. Eight-week-old mice underwent sham surgery, castration, or castration followed by testosterone-repletion (2.5 mg/kg/d initiated 1 wk after castration). Ten-wk-old intact TRAMP mice exhibit early multifocal prostatic intraepithelial neoplasia (PIN). Of the 200 prostate cancer-related genes measured by quantitative NanoString®, 189 are detectable, 164 significantly differ by genotype, 179 by testosterone status, and 30 by diet type (P<0.05). In TRAMP, expression of Birc5, Mki67, Aurkb, Ccnb2, Foxm1, and Ccne2 is greater compared to WT and is decreased by castration. In parallel, castration reduces Ki67-positive staining (P<0.0001) compared to intact and testosterone-repleted TRAMP mice. Expression of genes involved in androgen metabolism/signaling pathways are reduced by lycopene feeding (Srd5a1) and by tomato-feeding (Srd5a2, Pxn, and Srebf1). Additionally, tomato-feeding significantly reduced expression of genes associated with stem cell features, Aldh1a and Ly6a, while lycopene-feeding significantly reduced expression of neuroendocrine differentiation-related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early stages of prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk.