Acetylation on critical lysine residues of Apurinic/apyrimidinic endonuclease 1 (APE1) in triple negative breast cancers.

Protein acetylation plays many roles within living cells, modulating metabolism, signaling and cell response to environmental stimuli, as well as having an impact on pathological conditions, such as cancer pathogenesis and progression. The Apurinic/apyrimidinic endonuclease APE1 is a vital protein that exerts many functions in mammalian cells, acting as a pivotal enzyme in the base excision repair (BER) pathway of DNA lesions, as transcriptional modulator and being also involved in RNA metabolism. As an eclectic and abundant protein, APE1 is extensively modulated through post-translational modifications, including acetylation. Many findings have linked APE1 to cancer development and onset of chemo- and radio-resistance. Here, we focus on APE1 acetylation pattern in triple negative breast cancer (TNBC). We describe the validation and characterization of a polyclonal antibody that is specific for the acetylation on lysine 35 of the protein. Finally, we use the new antibody to analyze the APE1 acetylation pattern on a cohort of TNBC specimens, exploiting immunohistochemistry. Our findings reveal a profound deregulation of APE1 acetylation status in TNBC, opening new perspectives for future improvements on treatment and prognosis of this molecular subtype of breast carcinomas.