HEMEOXIGENASE-1 GENETIC VARIANTS EFFECTS ON BREAST CANCER PROGRESSION

SCHWEITZER, K.; ALONSO, E.G.; MASCARÓ, M.; FERNÁNDEZ CHÁVEZ, L.; COLÓ, G.P.; ALONSO, E.N.; FERRONATO, M.J.; FERMENTO, M.E.; CURINO, A.C.; FACCHINETTI, M.M.

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencia; 2022

Sociedad Argentina de Investigaciones Clínicas

Hemoxygenase-1 (HO-1) is a microsomal enzyme that catalyzes the degradation of the heme group, and its C-terminal truncated form can translocate to the nucleus and perform functions at the transcriptional level. Our laboratory has already shown that HO-1 has antitumoral effects in breast cancer. We have additionally confirmed that the HO-1 truncated form is not enzymatically active. The aim of this work was to study the effect of genetic overexpression of HO-1 variants (full-length form (FL), full-length form without enzymatic activity (H25A) and nuclear truncated form (T-HO1)) on cellular processes related to cancer development, and also the molecular mechanisms through which HO-1 would modulate the cellular processes investigated. To accomplish this goal, we used T47D human breast cancer cell line that was stably transfected with plasmids overexpressing HO-1 variants. To analyse cell behaviour between variants, we performed viability assays and flow cytometry, and to quantify differential protein expression we used immunofluorescence and western blot. We observed significant differences in cell viability between wild-type T47D cells and T47D cells overexpressing HO-1 variants. We found that the wild-type form is more proliferative than the FL-, H25A- and T-HO1-overexpressing forms (p