Proteomic changes induced by effective chemopreventive ratios of n-3:n-6 fatty acids and tamoxifen against MNU-induced mammary cancer in the rat

Christine G. Skibinski, Henry J. Thompson, Arunangshu Das, Andrea Manni, James D. Bortner, Anne Stanley, Bruce A. Stanley, Karam El-Bayoumy

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)979-988
Number of pages10
JournalCancer Prevention Research
Volume6
Issue number9
DOIs
StatePublished - Sep 1 2013

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Tamoxifen
Proteomics
Fatty Acids
Breast Neoplasms
Proteins
Diet
Chemoprevention
Vitamin D-Binding Protein
Far-Western Blotting
Gelsolin
14-3-3 Proteins
Haptoglobins
Apolipoproteins E
Lipid Metabolism
Neoplasms
Glycoproteins
Down-Regulation
Biomarkers
Clinical Trials
Inflammation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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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.",
author = "Skibinski, {Christine G.} and Thompson, {Henry J.} and Arunangshu Das and Andrea Manni and Bortner, {James D.} and Anne Stanley and Stanley, {Bruce A.} and Karam El-Bayoumy",
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Proteomic changes induced by effective chemopreventive ratios of n-3:n-6 fatty acids and tamoxifen against MNU-induced mammary cancer in the rat. / Skibinski, Christine G.; Thompson, Henry J.; Das, Arunangshu; Manni, Andrea; Bortner, James D.; Stanley, Anne; Stanley, Bruce A.; El-Bayoumy, Karam.

In: Cancer Prevention Research, Vol. 6, No. 9, 01.09.2013, p. 979-988.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Proteomic changes induced by effective chemopreventive ratios of n-3:n-6 fatty acids and tamoxifen against MNU-induced mammary cancer in the rat

AU - Skibinski, Christine G.

AU - Thompson, Henry J.

AU - Das, Arunangshu

AU - Manni, Andrea

AU - Bortner, James D.

AU - Stanley, Anne

AU - Stanley, Bruce A.

AU - El-Bayoumy, Karam

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