UC Riverside

Breast cancer is a highly molecular heterogeneous disease that drives different prognosis and treatment sensitivity. It is one of the most common cancers in women in the United States and accounts for about 25% of all cancer diagnoses in women worldwide. MYC is a powerful transcription factor that is highly regulated in normal physiological conditions through various mechanisms, such as posttranslational modifications (PTMs), for normal cell development, but becomes deregulated in oncogenic conditions. Therefore, deregulation of MYC has led to malignant transformation as observed in serval types of human cancers, but how this process determines tumor behavior is yet to be understood. PTMs, such as acetylation, ubiquitination, and phosphorylation, can affect MYC protein stability and function. In addition, MYC can be acetylated by different histone acetyltransferases (HATs), including p300, which preferentially acetylates MYC at lysine 149 (K149) and lysine 158 (K158), and GCN5 which acetylates lysine 323 (K323) via the STAGA complex. However, these modifications have distinct effects where p300-mediated acetylation increases MYC turnover, GCN5-mediated acetylation stabilizes the MYC protein. Yet, our understanding of MYC acetylation and how this process contributes to human cancer progression remains unclear. In human breast cancer, evidence has shown that epigenetic profiles vary across these distinct subtypes, yet the characterization of MYC acetylation remains unexplored. According to the lab’s previous results, MYC acetylation significantly increases when MYC is overexpressed in MCF10A transformed MYC cells compared to MCF10A non-transformed baseline expression. Therefore, we postulate that the patterns of acetylation of site-specific MYC lysine residues differ across breast cancer subtypes, influencing tumor behavior. In this study, I will analyze the role of MYC acetylation at specific lysine residues across distinct breast cancer subtypes and analyze how these modifications regulate select genetic programs.