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

FERMENTO ME; MARIANI F; ALONSO EN; GANDINI NA; GUEVARA JA; GRIOLI SM; FERRONATO MJ; COLO GP; MASCARO M; FACCHINETTI MM; CURINO AC

Mar del Plata

Congreso; LXIII congreso anual de la Sociedad Argentina de Investigación Clinica; 2018

Sociedad Argentina de Investigacion Clinica

Breast cancer (BC) is a heterogeneous disease with many subtypes that have different treatment responses and clinical outcomes, suggesting the need to find new molecular markers. We have previously shown that pharmacological inhibition of p300 displays anti-tumor activity in LM3 and MDA-MB-231 BC cell lines and in their respective murine models. Through genetic silencing of p300 in MDA-MB-231 cells we also demonstrated a decrease in cellular viability, migration, invasion and adhesion. We also showed that p300 silencing decreases cellular viability in LM3 cells and reduces the primary tumor growth in its syngeneic murine model. However, the role it plays in the metastatic process remained unknown. Therefore, in this work we aimed to study the effect of genetic silencing of p300 on tumor progression and invasion in LM3 cells and its syngeneic murine model. We obtained LM3 cells stably-overexpressing an shRNA for p300 (LM3-p300NEG) or its control plasmid (LM3-CTRL). The reduction in p300 levels was confirmed by RT-qPCR. We observed reduced cellular migration (wound healing assay), invasion (transwell with matrigel assay), adhesion (adhesion to the substrate assay) and an increase in the levels of E-cadherin and ß-catenin (WB) in LM3-p300NEG compared to LM3-CTRL (p