title: PPARβ mRNA expression, reduced by n-3 PUFA diet in mammary tumor, controls breast cancer cell growth.
abstract: The effect of numerous anticancer drugs on breast cancer cell lines and rodent mammary tumors can be enhanced by a treatment with long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) such as docosahexaenoic acid (DHA, 22:6n-3) which is a natural ligand of peroxisome proliferator-activated receptors (PPAR). In order to identify the PPAR regulating breast cancer cell growth, we tested the impact of siRNA, selected to suppress PPARα, PPARβ or PPARγ mRNA in MDA-MB-231 and MCF-7 breast cancer cell lines. The siPPARβ was the most effective to inhibit breast cancer cell growth in both cell lines. Using PPARα, PPARβ and PPARγ pharmacological antagonists, we showed that PPARβ regulated DHA-induced inhibition of growth in MDA-MB-231 and MCF-7 cells. In addition, the expressions of all 3 PPAR mRNA were co-regulated in both cell lines, upon treatments with siRNA or PPAR antagonists. PPAR mRNA expression was also examined in the NitrosoMethylUrea (NMU)-induced rat mammary tumor model. The expressions of PPARα and PPARβ mRNAs were correlated in the control group but not in the n-3 PUFA group in which the expression of PPARβ mRNA was reduced. Although PPARα expression was also increased in the n-3 PUFA-enriched diet group under docetaxel treatment, it is only the expression of PPARβ mRNA that correlated with the regression of mammary tumors: those that most regressed displayed the lowest PPARβ mRNA expression. Altogether, these data identify PPARβ as an important player capable of modulating other PPAR mRNA expressions, under DHA diet, for inhibiting breast cancer cell growth and mammary tumor growth.
authors.affiliation: Inserm UMR1069 "Nutrition, Croissance et Cancer", Faculté de Médecine, Université François Rabelais de Tours, France.
authors.forename: Ramez
authors.initials: R
authors.lastname: Wannous
authors.affiliation: Inserm UMR1069 "Nutrition, Croissance et Cancer", Faculté de Médecine, Université François Rabelais de Tours, France.
authors.forename: Emeline
authors.initials: E
authors.lastname: Bon
authors.affiliation: Inserm UMR1069 "Nutrition, Croissance et Cancer", Faculté de Médecine, Université François Rabelais de Tours, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Mahéo
authors.affiliation: Inserm UMR1069 "Nutrition, Croissance et Cancer", Faculté de Médecine, Université François Rabelais de Tours, France; Hôpital Bretonneau, CHU de Tours, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Goupille
authors.affiliation: Inserm UMR1069 "Nutrition, Croissance et Cancer", Faculté de Médecine, Université François Rabelais de Tours, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Chamouton
authors.affiliation: Inserm UMR1069 "Nutrition, Croissance et Cancer", Faculté de Médecine, Université François Rabelais de Tours, France; Hôpital Bretonneau, CHU de Tours, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bougnoux
authors.affiliation: Inserm UMR1069 "Nutrition, Croissance et Cancer", Faculté de Médecine, Université François Rabelais de Tours, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Roger
authors.affiliation: Inserm UMR1069 "Nutrition, Croissance et Cancer", Faculté de Médecine, Université François Rabelais de Tours, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Besson
authors.affiliation: Inserm UMR1069 "Nutrition, Croissance et Cancer", Faculté de Médecine, Université François Rabelais de Tours, France; Département de Biochimie, Faculté de Sciences Pharmaceutiques, Université François Rabelais de Tours, France. Electronic address: stephan.chevalier@univ-tours.fr.
authors.forename: Stephan
authors.initials: S
authors.lastname: Chevalier
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy; D048068:PPAR-beta / Q000235:genetics*; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D043823:Taxoids / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D015525:Fatty Acids, Omega-3; D048068:PPAR-beta; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; D043823:Taxoids; D000077143:Docetaxel
keywords: Breast tumor; DHA; MCF-7; MDA-MB-231; PPAR; n−3 PUFA