THU480 Loss Of Selenof And A Western Diet Promote Mammary Tumorigenesis

Disclosure: B. Flowers: None. A. Zigrossi: None. A. Diamond: None. I. Kastrati: None. SELENOF is an understudied selenium-containing protein which has previously been postulated to behave as a tumor suppressor in the breast. Examination of patient databases showed that SELENOF levels were lowest in tumors from patients with aggressive late-stage breast cancers. Whether loss of SELENOF drives breast tumorigenesis remains to be determined. To address this question, we used juvenile female wild type or systemic Selenof knockout mice and exposed them to 7,12-Dimethylbenz[a]anthracene (DMBA), a carcinogen which replicates the multistep process of breast tumorigenesis. Previous reports have shown that loss of Selenof led to glucose and metabolic dysregulation in mice suggesting a link between Selenof and metabolism. Because obesity is a risk factor in breast cancer, we challenged the mice with a western diet, high in fats and in calories, to mimic obesity. We hypothesized that loss of Selenof would promote DMBA-induced tumorigenesis and the western diet would exacerbate it. We found that tumor incidence was in fact highest in the Selenof knockout mice and western diet group. The Selenof knockout mice exhibited higher weights and higher fasting glucose levels consistent with metabolic dysfunction. These findings indicate that lower or loss of SELENOF expression may predispose a subset of women, especially obese ones, to increased risk of breast cancer. The link between SELENOF, obesity, and breast cancer warrants further investigation. Presentation: Thursday, June 15, 2023