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

Scope: 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. Methods and results: 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. Conclusion: 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. Ovarectomized athymic nude mice at 28 days of age were randomly assigned to four groups: soy flour (MS), purified isoflavone mix (MI), negative control (NC) and positive control (PC). MS and MI groups contained equivalent amounts of genistein, and both PC and NC groups received no genistein. All mice were fed AIN93G diet, with corn oil substituted with soy oil. Mice in the PC group received 2 milligram estradiol (E2) pellets and mice in the NC group received sham pellets. AIN93G based MI and MS diets contained 750 ppm genistein aglycone and were individually formulated and balanced to contain equal amounts of protein, carbohydrate and fat. All mice were euthanized 12 weeks after inoculation of MCF-7 tumor cells and tumors were immediately frozen by submersion into liquid nitrogen. All of the experimental procedures were approved by the Illinois Institutional Animal Care and Use Committee (Protocol ID 13315) and were conducted in accordance with the regulations described in the Committee’s Manual.