title: n-3 polyunsaturated fatty acids and HER2-positive breast cancer: interest of the fat-1 transgenic mouse model over conventional dietary supplementation.
abstract: Overexpression of the tyrosine kinase receptor ErbB2/HER2/Neu, occurs in 25%-30% of invasive breast cancer (BC) with poor patient prognosis. Even if numerous studies have shown prevention of breast cancer by n-3 fatty acid intake, the experimental conditions under which n-3 fatty acids exert their protective effect have been variable from study to study, preventing unifying conclusions. Due to confounding factors, inconsistencies still remain regarding protective effects of n-3 polyunsaturated fatty acids (PUFA) on BC. When animals are fed with dietary supplementation in n-3 fatty acids (the traditional approach to modify tissue content and decrease the n-6/n-3 ratio) complex dietary interactions can occur among dietary lipids (antioxidants, vitamins…) that can modulate the activity of n-3 fatty acids. So, what are the specific roles of these n-3 PUFA in reducing breast cancer risk and particularly preventing HER2-positive breast cancer? In this review, we discuss crucial points that may account for discrepancies of results and provide a highly effective genetic approach that can eliminate confounding factors of diet for evaluating the molecular mechanisms of n-3 PUFA in HER2 signaling pathway regulation. The fat-1 transgenic mouse model is capable of converting n-6 to n-3 fatty acids leading to an increase in n-3 fatty acid content with a balanced n-6/n-3 fatty acid ratio in all tissues. The fat-1 mouse model allows well-controlled studies in HER2-positive breast cancer prevention to be performed, without the conflict of potential confounding factors of diet.
authors.affiliation: Université de Bourgogne, UFR Sciences de la Vie, de la Terre et de l'Environnement, 6 Boulevard Gabriel, 21000 Dijon, France; INSERM UMR U866 Lipides Nutrition Cancer, Université de Bourgogne, 6 Boulevard Gabriel, 21000 Dijon, France.
authors.forename: Zuquan
authors.initials: Z
authors.lastname: Zou
authors.forename: Célia
authors.initials: C
authors.lastname: Bidu
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bellenger
authors.forename: Michel
authors.initials: M
authors.lastname: Narce
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bellenger
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000378:metabolism* / Q000517:prevention & control; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D019587:Dietary Supplements; D004195:Disease Models, Animal; D044943:Fatty Acid Desaturases / Q000235:genetics; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000502:physiology*; D005260:Female; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
chemical_list: D016588:Anticarcinogenic Agents; D029742:Caenorhabditis elegans Proteins; D044943:Fatty Acid Desaturases; D015525:Fatty Acids, Omega-3; D018719:Erb-b2 Receptor Tyrosine Kinases; C466741:fat-1 protein, C elegans; C508053:ERBB2 protein, human
keywords: Fat-1 transgenic mouse model; HER2-positive breast cancer; n-3 fatty acids