Abstract 1264 Characterizing the role of SMC2 in normalized mammary epithelial cells

Breast cancer is a heterogenous disease and is divided into subtypes based on hormone receptor expression. Triple Negative Breast Cancers (TNBC) lack these, and thus have limited targeted therapeutic options. TNBC is hallmarked by its aggressive nature and increased metastasis, contributing to worse patient outcomes. Many treatments for patients with TNBC carry elevated risk for recurrence and resistance, making the exploration of new therapeutic options necessary. Our lab has investigated the role of Structural Maintenance of Chromosomes 2 (SMC2), a core member of the condensin complex, in TNBC cells. SMC2 is responsible for maintaining genomic integrity, and our data has shown that in TNBC cells, SMC2 silencing increases chromosomal instability (CIN) phenotypes, decreases cell growth, and increases cell migration. CIN is a trait of numerous cancers that advances tumor cell accumulation of genetic defects. We hypothesize that SMC2 loss will not induce the same effects in normalized mammary epithelial cells as displayed in TNBC cells. To begin to test this hypothesis, SMC2 was silenced in normalized mammary epithelial cells. We identified that SMC2 loss prompts an increase in CIN phenotypes including multinucleation and dysmorphic nucleation, as well as an increase in cell migration and a reduction in cell growth, indicating that the effects are similar to TNBC cells. Future studies will explore the effects of silencing SMC2 in a variety of different cell types.