Study of the role of p300 in the development and progression of breast cancer

Abstract

Breast cancer (BC), especially triple negative BC (TNBC), is a heterogeneous disease with many subtypes that has different treatment responses and clinical outcomes, suggesting the need to find new molecular markers. Recently, an increasing body of evidence indicates that p300 could play a role in cancer. Nonetheless, the role of the protein in this disease remains unclear, since there is evidence indicating that it can function both as a tumor suppressor and as an oncoprotein. Elsewhere we demonstrated that pharmacological inhibition of p300 acetylase function has an antitumoral role in the murine hormone-independent (HI) BC LM3 cell line, and decreases tumor progression in the syngeneic murine model of LM3. In addition, we showed that the presence of p300 in the cytoplasm correlates with increased survival of patients with BC. As these results were obtained by pharmacological modulation of p300, we decided to investigate the genetic modulation of p300 in the LM3 cell line and its syngeneic murine model. Furthermore, knowing that TNBC has an aggressive clinical behavior, poor prognosis and lack of targeted therapies, we decided to study the expression of p300 in human TNBC.