Isoflavones in soy flour diet have different effects on whole-genome expression patterns than purified isoflavone mix in human MCF-7 breast tumors in ovariectomized athymic nude mice.

Isoflavones in soy flour diet have different effects on whole-genome expression patterns than purified isoflavone mix in human MCF-7 breast tumors in ovariectomized athymic nude mice.
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DOI:
10.1002/mnfr.201500028
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发表时间:
2015-08
影响因子:
5.2
通讯作者:
Helferich WG
Helferich WG
中科院分区:
农林科学2区
文献类型:
--
作者:
Liu Y;Hilakivi-Clarke L;Zhang Y;Wang X;Pan YX;Xuan J;Fleck SC;Doerge DR;Helferich WG

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豆粉饮食(MS)阻止异黄酮刺激胸腺裸鼠MCF-7肿瘤生长,表明大豆中的其他生物活性化合物可以抵消异黄酮的雌激素特性。本文研究了解释食用大豆粉的保护作用的潜在信号转导途径。用MCF-7人乳腺癌细胞接种去卵巢的胸腺裸鼠,分别饲喂含有等量染料木素的MS或纯化异黄酮混合物(MI)。阳性对照组给予雌二醇微丸,阴性对照组给予假微丸。采用GeneChip-Human-Genome-U133-Plus-2.0 Array平台评估基因表达,并采用生物信息学方法对结果进行分析。ms喂养小鼠的肿瘤中,肿瘤生长抑制基因ATP2A3和BLNK的表达较高,癌基因MYC的表达较低。mi喂养小鼠的肿瘤表达较高水平的致癌基因MYB和较低水平的MHC-I和MHC-II,使肿瘤细胞逃避免疫监视。在雌激素受体阳性乳腺癌患者中,ms诱导的基因表达改变预示着生存期的延长,而mi诱导的基因改变预示着生存期的缩短。我们的研究结果表明,膳食大豆粉对基因表达的影响不同于纯化异黄酮,这可能解释了为什么大豆食品可以防止异黄酮诱导的MCF-7肿瘤生长。
Soy flour diet (MS) prevented isoflavones from stimulating MCF-7 tumor growth in athymic nude mice, indicating that other bioactive compounds in soy can negate the estrogenic properties of isoflavones. The underlying signal transduction pathways to explain the protective effects of soy flour consumption were studied here. Ovariectomized athymic nude mice inoculated with MCF-7 human breast cancer cells were fed either MS or purified isoflavone mix (MI), both with equivalent amounts of genistein. Positive controls received estradiol pellets and negative controls received sham pellets. GeneChip-Human-Genome-U133-Plus-2.0 Array platform was used to evaluate gene expressions, and results were analyzed using bioinformatics approaches. Tumors in MS-fed mice exhibited higher expression of tumor-growth-suppressing genes ATP2A3 and BLNK, and lower expression of oncogene MYC. Tumors in MI-fed mice expressed higher level of oncogene MYB and lower level of MHC-I and MHC-II, allowing tumor cells to escape immunosurveillance. MS-induced gene expression alterations were predictive of prolonged survival among estrogen-receptor-positive breast cancer patients, whilst MI-induced gene changes were predictive of shortened survival. Our findings suggest dietary soy flour affects gene expression differently than purified isoflavones, which may explain why soy foods prevent isoflavones-induced stimulation of MCF-7 tumor growth in athymic nude mice.
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