Abstract 1354: Chronic social stress in a mouse model of triple-negative breast cancer is associated with oncogenic changes in mammary fat.

Abstract

Abstract Chronic social isolation is linked to increased mammary tumor growth in rodent models of breast cancer. In the C3(1)/SV40 T-antigen (Tag) FVB/N mouse model of “triple-negative” breast cancer, the heightened stress response elicited by social isolation has been associated with increased expression of metabolic genes in the mammary gland before invasive tumors develop (i.e. during the in situ carcinoma stage). To further understand how underlying accelerated mammary tumor growth is associated with social isolation, we separated the mammary gland adipose tissue from adjacent ductal epithelial cells and analyzed individual cell types for changes in metabolic gene expression. Specifically, increased expression of the key metabolic genes Acaca, Hk2 and Acly was found primarily in the adipocyte, rather than epithelial fraction. Increased metabolic gene expression in the mammary adipocytes of socially isolated mice coincided with increased glucose metabolism, lipid synthesis, and leptin expression. Furthermore, culture media from isolated mouse mammary adipose tissue resulted in relatively increased proliferation and decreased apoptosis of mammary epithelial cancer cells derived from the same mouse strain. Additional gene expression analyses identified significant upregulation of the novel carbohydrate response element binding protein beta isoform (CHREBP-β) in socially isolated mammary fat. We hypothesize that the response to social isolation induces metabolic changes in mammary fat that are coordinated through CHREBP-β and are pro-oncogenic. We are currently performing global lipidomic and metabolomic analyses of mammary adipose tissue and secreted culture media to identify bioactive molecules involved in tumor growth. Citation Format: Paul A. Volden, Erin Wonder, Maxwell Skor, Feenalie Patel, Martha McClintock, Matthew Brady, Suzanne Conzen. Chronic social stress in a mouse model of triple-negative breast cancer is associated with oncogenic changes in mammary fat. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1354. doi:10.1158/1538-7445.AM2013-1354