Abstract 5578: Transcriptomic changes in tamoxifen-treated mammary tumors in Sprague-Dawley rats fed with omega-3 or omega-6 rich diets
Authors: Bidinotto Lucas T. , Vanegas Johana E. , Vanden Heuvel John P. , de Cicco Ricardo Lopez , Santucci-Pereira Julia , Washington Sharlene , Xu Haifang , Russo Irma H. , El-Bayoumy Karam , Manni Andrea , Russo Jose 
Published: June 2012

Abstract
We have demonstrated that administration of an omega-3 rich diet to Tamoxifen (Tam)-treated rats reduced the incidence of mammary tumors when compared to rats fed an omega-6 rich diet in the presence and in the absence of Tam treatment (A. Manni, et al. Cancer Prev Res 3:322, 2010). To understand the mechanisms of antitumor action of omega-3 fatty acids, we evaluated the transcriptomic changes in 1-Methyl-1-nitrosourea (MNU)-induced mammary tumors in Tam-treated rats fed with omega-3 (fish oil) or omega-6 (corn oil) fatty acids. Twenty one-days old Sprague Dawley rats received a single 50 mg/kg of body weight (bw) i.p. injection of MNU and were distributed into 4 groups: 1) CO group (20% corn oil diet); 2) COtam group (20% CO diet plus Tam 100 μg/Kg bw s.c., 5 days/week); 3) FO group (17% fish oil diet); 4) FOtam group (17% FO diet plus Tam). Animals were euthanized 8 weeks after MNU injection. RNA from cribiform tumors was extracted and Agilent oligonucleotide microarrays were performed in three samples per group. Tam-treated groups were compared to their respective controls (FOtam vs. FO and COtam vs. CO). Additionally, the FO-treated group was compared to the CO-treated group. Genes were considered differentially expressed when their level of expression differed by at least 3-fold with a P value &lt;0.01. Genes of interest were validated by real time PCR.
We found 32 differentially expressed genes between COtam and CO, 58 differentially expressed genes between FOtam and FO, and 19 differentially expressed genes between FO and CO. Real time PCR confirmed the differential expression of SerpinB10, Wisp2 and Apod in the FO-treated groups, which may be related to greater tumor differentiation. The down-regulation of Thrsp and Wnt5b genes in FOtam group may be related to tumor growth impairment and lower capacity of metastasis. Moreover, the up-regulation of IRF7, RT1-CE3, RT1-CE16 and RT1-Aw2 points to an improvement of the immune response against tumors in FO-treated animals. However, the up-regulation of FCER1A, HDC, MS4A2, SLP1, MCPT1 and MCTP2 suggests a shift of the immune response towards a Th2 pattern (mast cell-based immune response), which could be a mechanism of escape from the immune response caused by the combination of FO and Tam treatment. Our data suggests that an omega-3 rich diet could lead to a more differentiated tumor phenotype and an improved immune response against tumors. However, the administration of tamoxifen to FO fed rats promoted a Th2 pattern of immune response, which could represent an escape mechanism of the tumor cells from the improved immune response caused by FO per se. (Supported by the Susan G. Komen for the Cure, grant KG081632).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5578. doi:10.1158/1538-7445.AM2011-5578