title: Proteomic changes induced by effective chemopreventive ratios of n-3:n-6 fatty acids and tamoxifen against MNU-induced mammary cancer in the rat.
abstract: We used a proteomic approach to gain insights into the mechanisms of protection at the protein level by a high n-3:n-6 ratio in the absence and presence of Tamoxifen. Four groups were treated with 1-methyl-1-nitrosourea (MNU) and fed the following diets with varied n-3:n-6 ratios; group 1 = 1:1; groups 2 and 3 = 10:1 and 25:1, respectively; group 4: (25:1) plus Tamoxifen (1 mg/kg diet). The plasma from six rats/group was pooled and analyzed with the isobaric tags for relative and absolute quantitation method; 148 proteins were identified with 95% confidence by ProteinPilot 4.0. In plasma of rats fed 10:1, 25:1 n-3:n-6, and 25:1 plus Tamoxifen, the number of proteins that met our criteria (P ≤ 0.05, error factor ≤ 2) were 10, 14, and 19 proteins, respectively. Selected proteins were further validated by Western blotting. Compared to 1:1, both 10:1 and 25:1 diets upregulated vitamin D binding protein, gelsolin, and 14-3-3 sigma, reported to have tumor suppressive effects, whereas alpha-1B-glycoprotein, which has been reported to be elevated in the serum of breast cancer patients was decreased. Compared to 25:1, the 25:1 plus Tamoxifen diet downregulated apolipoprotein E, haptoglobin, and inter-α-inhibitor H4 heavy chain. Ingenuity pathway analysis determined that the trends of specific proteins were related to lipid metabolism in the 25:1 n-3:n-6 group, whereas the 25:1 n-3:n-6 plus Tamoxifen group included proteins involved in cancer and inflammation. Our results show that several proteins were altered in a manner consistent with chemoprevention. Such proteins may serve as biomarkers to monitor efficacy of n-3 and Tamoxifen in future clinical chemoprevention trials.
authors.affiliation: Departments of Biochemistry & Molecular Biology, Penn State University College of Medicine, PA 17033, USA.
authors.forename: Christine G
authors.initials: CG
authors.lastname: Skibinski
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Thompson
authors.forename: Arunangshu
authors.initials: A
authors.lastname: Das
authors.forename: Andrea
authors.initials: A
authors.lastname: Manni
authors.forename: James D
authors.initials: JD
authors.lastname: Bortner
authors.forename: Anne
authors.initials: A
authors.lastname: Stanley
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Stanley
authors.forename: Karam
authors.initials: K
authors.lastname: El-Bayoumy
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004032:Diet; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D008770:Methylnitrosourea / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D000477:Alkylating Agents; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D043371:Fatty Acids, Omega-6; D013629:Tamoxifen; D008770:Methylnitrosourea