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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #208290
Title: Prepubertal Changes in Lipid Homeostasis Gene Expression in Mammary Glands of Rats Exposed to Dietary Soy

Author
item SU, YING - ACNC/UAMS
item SIMMEN, FRANK - ACNC/UAMS
item XIAO, RIJIN - ACNC/UAMS
item SIMMEN, ROSALIA - ACNC/UAMS

Submitted to: Endocrine Society Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 2/15/2007
Publication Date: 6/2/2007
Citation: Su, Y., Simmen, F.A., Xiao, R., Simmen, R.C. 2007. Prepubertal changes in lipid homeostasis gene expression in mammary glands of rats exposed to dietary soy [abstract]. The Endocrine Society, 89th Annual Meeting, June 2-5, 2007, Toronto, Canada. 2007 CDROM, Program No. P1-250.

Interpretive Summary: The linkage between nutrition and cancer prevention has been widely studied. In our lab, we have shown lifetime consumption of soy diet is protective in a rat carcinogen-induced breast cancer model. Mammary gland gene expression of weanling rats that were fed with soy diet had dramatic effects on local fat metabolism and stress hormone-glucocorticoid regulation. We suspect that these early changes may lead to greater mammary tissue differentiation (a more mature mammary gland) which is more resistant to development of cancer. Future studies will explore this line of research and will define the dietary factors in soy responsible for these effects.

Technical Abstract: 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. Of the 8 genes down-regulated by SPI, 4 are involved in lipid homeostasis: malic enzyme 1, fatty acid synthase (Fasn), stearoyl CoA desaturase-1 (Scd1), and insulin-induced gene 1. One of five SPI-induced genes is 11beta-hydroxysteroid dehydrogenase 1 (Hsd1), which converts 11beta-dehydrocorticosterone to corticosterone, and is associated with increased lipolysis. Quantitative RT-PCR confirmed that Fasn (p=0.05) and Scd1 (p=0.01) transcipt levels were lower for SPI than CAS in PND21 mammary gland, but were up-regulated for SPI relative to CAS (Fasn, p=0.01; Scd1, p=0.038) at PND50. The greater Hsd1 transcript levels observed for SPI at PND21 (p=0.043) were maintained at PND50 (p=0.023). Results suggest that changes in lipid homeostasis occurring in the mammary fat pad during postnatal development are influenced by diet. The significance of early changes in stromal functions, possibly mediated by glucocorticoids, in the regulation of growth and differentiation of the mammary epithelium leading to breast cancer resistance, warrants further investigation.