Breast cancer has the second-highest cancer mortality rate for women in the United States. There are effective therapies available and a growing list of biomarkers for prognosis. However, new breast cancer targets are critically needed for patients refractory to available therapies. The present study evaluates the role of gap 0 switch 2 (G0S2), in breast cancer. Using online databases, we observed G0S2 expression is downregulated in patients with estrogen receptor-positive (ER+) breast cancer and patients with high G0S2 expression have a lower rate of relapse after treatment. Previously, our lab showed G0S2 overexpression in ER+ breast cancer cell lines resulted in decreased proliferation. Further knockout of G0S2 in murine embryonic fibroblast resulted in higher oncogenic transformation and resistance to mTOR inhibitors. These results suggest that G0S2 has a tumor suppressive function in ER+ breast cancer. To test whether G0S2 has a role in ER-negative breast cancer global knockout of G0S2 was engineered in the ER-negative MMTV-PyMT transgenic mouse model. Slower tumor progression and decreased lung metastasis was observed in G0S2-null transgenic females compared to wild-type transgenic females. These data suggest that the role of G0S2 in breast cancer in dependent on ER-status, where G0S2 functions as a tumor suppressor in ER-positive breast cancer and a tumor promoter in ER-negative breast cancer. Molecular and genetic studies manipulating G0S2 and ER in various breast cancer contexts are ongoing and will help elucidate that precise role of G0S2 in breast cancer and provide clarity on the potential of G0S2 as a novel prognostic marker and therapeutic target.

Citation Format: Andrea K. Corbet, Emmanuel Bikorimana, Ratnakar Singh, Zeeshan Fazal, Raya I. Boyd, Sarah Freemantle, Michael J. Spinella. Elucidating the role of G0S2 in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2488.