HO1 plays an important role in iron metabolism alteration in breast cancer cells.

GIORGI, G; GANDINI, NA; FACCHINETTI, MM; CURINO, AC; ROQUE, ME

Mar del Plata

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019; 2019

Sociedad Argentina de Investigación Clínica

Heme Oxygenase-1 (HO1) catalyzes heme degradation, yielding biliverdin, carbon monoxide and iron. When iron is in excess produces oxidative stress through reactive oxygen species (ROS) generation. Since both HO1 and iron metabolism disruptions have been related to breast cancer progression, we sought to investigate how tumor cells regulate iron metabolism when HO-1 expression is altered. For this purpose we first investigated the correlation of HO1 with several iron proteins by using in silico analyses and corroborated the strongest hits by using immunohistochemistry (IHC) performed on human biopsies (n=33). In addition, a syngeneic model of LM3 and a xenograft model of MDA-MB-231 cells stably overexpressing HO1 were used to study these hits. We further performed in culture analyses using LM3 breast cancer cells treated with hemin (H), vehicle or the combination with an antioxidant, and studied iron storage (Prussian Blue), ROS levels (DFCA) and cell cycle progression (flow cytometry). In silico analyses showed that HO1 correlated with DMT1 (p=9.8e-05), ZIP14 (p=4.2e-06), Prohepcidin (p=1.4e-12) and L-ferritin (p=2.2e-16). In order to study the correlation between HO1 and DMT1 in breast cancer we analyzed by IHC their expression in biopsies. We observed an inverse correlation between DMT1 and HO1 expression (p