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Identification of gene networks underlying mammary tumor protection by dietary exposure to soy and genistein
Author(s) -
Su Ying,
Xiao Rijin,
Geng Yan,
Skinner Charles M,
Simmen Frank A,
Simmen Rosalia CM
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a560-d
Subject(s) - biology , genistein , pten , carcinogenesis , gene , gene expression , mammary gland , soy protein , estrogen receptor , endocrinology , medicine , signal transduction , cancer , genetics , breast cancer , biochemistry , pi3k/akt/mtor pathway
We have previously shown that lifetime consumption of soy protein isolate (SPI) reduced the incidence of chemically‐induced mammary tumors in young adult rats, relative to those fed the control diet containing Casein (CAS). Genistein (GEN) is a biologically active component of soy foods and is associated with reduced breast cancer risk in women who consume soy‐rich diets. To obtain insights into the molecular mechanisms underlying tumor protection by these dietary components, global gene expression profiles of mammary epithelial cells (MEC) isolated from postnatal day 50 rats fed AIN‐93G diets with CAS ± GEN or SPI were determined using Affymetrix RAE230A microarrays representing 14,280 genes. We identified 18 induced and 34 repressed genes in the SPI‐fed group, and 36 induced and 53 repressed genes in the GEN‐fed group, relative to CAS (>1.5‐fold difference, P<0.05). MEC from GEN‐fed rats had 43 higher and 31 lower expressed genes, than those of SPI‐fed rats. The expression patterns of: a) Egr3, quiescin 6, Transferrin Receptor, cadherin 22, estrogen receptor‐α, PTEN (SPI=GEN >CAS); b) sFRP2, WAP (GEN>SPI=CAS); and c) progesterone receptor (SPI>CAS=GEN) genes were validated using real‐time quantitative RT‐PCR. Results demonstrate marked GEN effects on gene expression that are not mimicked by SPI. The identification of transcripts co‐ or differentially‐regulated by SPI and GEN suggests common and unique signaling pathways underlying nutritional prevention of mammary tumorigenesis. (USDA‐CRIS‐6251‐5100‐002‐06S).