Effect of pharmacological inhibition of p300 on the expression and localization of p53 in triple negative breast cancer

GALLARDO G.A.; CLEMENTE V.; FERRONATO M.J.; ALONSO E.N.; COLO G.P.; FACCHINETTI M.M.; FERMENTO M.E.; CURINO A. C.

Mar del Plata

Congreso; LXVIII Reunión Anual de la Sociedad Argentina de Investigación clínica (SAIC).; 2023

Sociedad Argentina de Investigación clínica (SAIC).

Triple-negative breast cancer (TNBC) is a heterogeneous group oftumors that lack specific molecular targets. Therefore, it is necessary to investigate potential tumor markers for this subtype of BC. Arelationship between p300 and cancer has been demonstrated; butits role remains unclear, as it has been documented both as a tumorsuppressor and an oncoprotein. p300 functions as a transcriptional coactivator, histone acetyltransferase, and acetylates lysines ofproteins involved in functions beyond transcription. This protein actsas a transcriptional coactivator of p53, regulating its activity throughacetylation mechanisms in various tumor types. Hence, we decided to study whether the regulation of p53 mediated by p300 caninfluence its cellular localization and the alteration of its functionsin TNBC. The aim of this work was to evaluate the effect of pharmacological inhibition of p300 on the expression and localizationof p53 in TNBC cell lines (MDA-MB-231 and 4T1). The cell lineswere treated with VV59 (an inhibitor of p300 acetylase function)or DMSO (vehicle) for 24 hours. In western blot assays, no significant differences were observed in p53 expression levels in eithercell lines. However, a decrease in acetylated p53 levels was notedin the MDA-MB-231 cells treated with VV59 compared to controlcells (p=0.0370). Through immunofluorescence, we observed thatp300 inhibition reduced nuclear expression and localization of p53(p