Lifelong n-3 Polyunsaturated Fatty Acid Exposure Modulates Size of Mammary Epithelial Cell Populations and Expression of Caveolae Resident Proteins in Fat-1 Mice

Nutrients. 2019 Oct 15;11(10):2477. doi: 10.3390/nu11102477.

Abstract

Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been associated with reduced breast cancer risk; however, the exact mechanism remains elusive. Female wildtype (WT) and fat-1 mice were fed a 10% safflower diet until 6 weeks of age. Mammary gland epithelial cells (EC) were isolated and EC populations were determined by CD24 surface expression. Fat-1 mice expressed 65%, 20%, and 15% while WT mice expressed 65%, 26% and 9% for non-, myo- and luminal ECs, respectively. The luminal EC population was significantly greater in fat-1 mice (p ≤ 0.05), while the total number of mammary ECs were similar between groups (p = 0.79). Caveolae was isolated from ECs and Her-2/neu, ER-α and cav-1 protein expression was determined by Western blotting. Fat-1 mice had a two-fold greater ER-α (p ≤ 0.05) and a 1.5-fold greater cav-1 (p ≤ 0.05) expression than WT with a similar amount of Her-2/neu protein (p = 0.990) between groups. Overall, this study provides novel mechanistic evidence by which n-3 PUFA modifies early mammary gland development that may potentially reduce breast cancer risk later in life.

Keywords: ER-α; Her-2/neu; breast cancer; caveolae; fat-1 mice; n-3 PUFA.

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / prevention & control
  • CD24 Antigen / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Caveolae / drug effects*
  • Caveolae / metabolism
  • Caveolin 1 / metabolism
  • Dietary Supplements*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Estrogen Receptor alpha / metabolism
  • Fatty Acid Desaturases / genetics
  • Fatty Acid Desaturases / metabolism
  • Fatty Acids, Omega-3 / administration & dosage*
  • Female
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / drug effects*
  • Mammary Glands, Animal / metabolism
  • Mice, Transgenic
  • Phenotype
  • Receptor, ErbB-2 / metabolism

Substances

  • CD24 Antigen
  • Caenorhabditis elegans Proteins
  • Cav1 protein, mouse
  • Caveolin 1
  • Cd24a protein, mouse
  • Esr1 protein, mouse
  • Estrogen Receptor alpha
  • Fatty Acids, Omega-3
  • fat-1 protein, C elegans
  • Fatty Acid Desaturases
  • Erbb2 protein, mouse
  • Receptor, ErbB-2