Heme oxygenase-1 modulates breast cancer progression

NORBERTO A GANDINI; MARÍA E. FERMENTO; MARÍA M. FACCHINETTI ; ALEJANDRO C. CURINO

Miami

Congreso; 6th International congress on heme oxygenases; 2009

An increasing amount of evidence indicates that HO-1 activation may play a role in carcinogenesis and can potently influence the growth and metastasis of tumors. In breast cancer it has been shown to decrease proliferation and invasion. The aim of this work was to study the role of HO-1 in breast cancer progression. As a a first approach we tested HO-1 expression in human breast cancer specimens evaluating its correlation with patient survival. Immunohistochemistry for HO-1 was performed in tissue samples from 60 patients with primary breast cancer. We found positive staining in 73% of specimens and protein expression was stronger in tumor than in non-malignant adjacent area (Mann-Whitney U Test; p<0,05). Interestingly, HO-1 was detected in the nuclei in 22% of the samples expressing HO-1. Analysis of prognostic significance revealed that HO-1 positivity associates with better patient outcome as assessed by Kaplan Meier (log-rank test; p<0.05). In order to better study the significance of HO-1 in breast cancer, we assessed the role of HO-1 on cellular survival and migration by using primary tissue cultures from breast tumors belonging to a DMBA-induced rat mammary carcinoma model and also breast cancer cell lines. Upregulation of HO-1 by hemin resulted in reduced cell survival as assessed by MTT, whereas inhibition of enzyme activity by SnPP had the opposite effect. Flow cytometry was used to confirm these results. No significant modulation of either cyclin D or cyclin E levels was observed. Nuclear localization was also observed in these cells. Additionally, cell motility was affected by HO-1 modulation. Taken together, these results show that HO-1 expression is upregulated in human breast cancer specimens and suggest that HO-1 may play a role in breast cancer progression by modulating cell proliferation and migration.