Hemoxygenase-1 involvement in breast cancer

GANDINI NA; COLÓ GP; ALONSO EN; FERMENTO ME; MASCARO M; FERRONATO MJ; ABBA MC; AREVALO J; IVARRA A; BARRERA LAMAS N; CURINO AC; FACCHINETTI MM

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Simposio; The Fourth South American Symposium in Signal Transduction and Molecular Medicine (SISTAM); 2018

Heme oxygenase-1 (HO-1) is an enzyme involved in cellular responses to oxidative stress and has also been shown to regulate processes relates to cancer progression. In this regard, HO-1 has been shown to display a dual effect with either antitumor or protumor activity, being this also true for breast cancer (BC). On the other hand, it has been reported that HO-1 can translocate to multiple subcellular compartments and can have non-enzymatic signaling roles. Thus, in the nucleus the protein may act as a transcriptional co-regulator protein and can bind and modulate other important proteins. In this work we intended to address this discrepancy regarding the role of HO-! In BC. In vivo experiments showed that both pharmacological activation and genetic overexpression of HO-1 reduced the tumor burden in two different animal models of BC. Furthermore, the activation of HO-1 in several BC cell lines reduced cellular viability by inducing apoptosis (p˂0.05) and cell cycle arrest (p˂0.003) and decreased the cellular migration, invasion and adhesion rates by modulating pathways involved in the epithelial-mesenchymal transition. Furthermore, HO-1 activation impaired in vivo the metastatic dissemination (p=0.020). In addition, the enzymatic activity of HO-1in nuclear and cytoplasm tic fraction was studied by ICP-AES. In conclusion, we demonstrated that HO-1 displays antitumor activities in BC. Furthermore, our studies suggest that HO-1 subcellular localization may explain the differential effects observe for the protein in different tumor types.