Early soy exposure via maternal diet regulates rat mammary epithelial differentiation by paracrine signaling from stromal adipocytes

J Nutr. 2009 May;139(5):945-51. doi: 10.3945/jn.108.103820. Epub 2009 Mar 25.

Abstract

Diet-mediated changes in transcriptional programs that promote the early differentiation of the mammary gland may lead to reduced breast cancer risk. The disparity in adult breast cancer incidence between Asian women and Western counterparts is attributed partly to high soy food intake. Here, we conducted genome-wide profiling of mammary tissues of weanling rats exposed to soy protein isolate (SPI) or control casein (CAS) via maternal diet to evaluate the contribution of early exposure on mammary gene expression. Of the identified 18 up- and 39 downregulated genes with SPI relative to CAS, a subset was associated with lipid metabolic pathways, consistent with reduced mammary adipocyte size and suggesting stromal adipocyte-specific genomic changes. Female offspring of rats fed SPI tended to have fewer terminal end buds (P = 0.06) and had significantly lower body weight and abdominal fat mass. To demonstrate the functional consequence of SPI-mediated adipocyte metabolic changes on neighboring mammary epithelium, the expression of in vivo regulated genes in 3T3-L1 adipocytes treated with soy isoflavone genistein and effects of the resultant conditioned medium (CM) on the differentiation of HC11 mammary epithelial cells were evaluated by quantitative RT-PCR and/or Western immunoblots. In differentiated 3T3-L1, genistein decreased fatty acid synthase and stearoyl-CoA desaturase and increased hydroxysteroid 11-beta dehydrogenase 1 expression. CM from genistein-treated adipocytes had higher adiponectin levels and augmented prolactin-induced, glucocorticoid-regulated beta-casein levels. These findings suggest that soy-associated components, by targeting mammary adipocytes, alter paracrine signaling to enhance mammary epithelial differentiation, with important implications for the prevention of breast cancer associated with obesity and obesity-related diseases.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Animals
  • Cell Differentiation / drug effects*
  • Culture Media, Conditioned / pharmacology
  • Dietary Proteins / administration & dosage*
  • Epithelial Cells / drug effects
  • Fatty Acid Synthases / genetics
  • Female
  • Gene Expression / drug effects
  • Genistein / pharmacology
  • Hydroxysteroid Dehydrogenases / genetics
  • Mammary Glands, Animal / cytology*
  • Maternal-Fetal Exchange*
  • Mice
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Soybean Proteins / administration & dosage*
  • Stearoyl-CoA Desaturase / genetics
  • Stromal Cells / metabolism
  • Weaning

Substances

  • Culture Media, Conditioned
  • Dietary Proteins
  • Soybean Proteins
  • Genistein
  • Hydroxysteroid Dehydrogenases
  • Stearoyl-CoA Desaturase
  • Fatty Acid Synthases