Influence of IFN-gamma and its receptors in human breast cancer

Background: Interferons are a group of proteins that trigger multiple responses including prevention of viral replication, inhibition of cell growth, and modulation of cell differentiation. In different mammary carcinoma cell lines IFN gamma induces growth arrest at mid-GI. At the present there are no in vivo studies in human breast. The aim of this study was to investigate the expression patterns of IFN gamma and its two receptors (IFN gamma-R alpha and IFN gamma-R beta) by Western blot and immunohistochemistry, in order to elucidate its role in the different types of human breast cancer (in situ and infiltrative). Methods: Immunohistochemical and semiquantitative study of IFN gamma, its receptors types (IFN gamma-R alpha and IFN gamma-R beta), cell proliferation (proliferating cell nuclear antigen, also named PCNA), and apoptosis (TUNEL method) was carried between the three breast groups (fibrocystic lesions, in situ tumors and infiltrating tumors). Results: In the three groups of patients, IFN gamma and IFN gamma-R alpha immunoreactions appeared in the cytoplasm while IFN alpha-R beta also was found in the nucleus. The optical density to IFN gamma was higher in in situ carcinoma than in benign and infiltrating tumors. When we observed IFN gamma-R alpha, the optical density was lower in infiltrating carcinoma than in benign and in situ tumors (the higher density). To IFN gamma-R beta, the optical density was similar in the three group samples. In tumor samples PCNA and TUNEL index was significantly higher; than in benign diseases. PCNA index increased with the malignance. No significant differences were found between cancer types to TUNEL. IFN gamma could be a potential therapeutic tool in breast cancer. However, tumor cells are able to escape from the control of this cytokine in the early tumor stages; this is probably due to a decreased expression of IFN gamma, or also to an alteration of either its receptors or some transduction elements. Conclusion: We conclude that the decrease in the % positive samples that expressed IFN gamma and IFN gamma-R alpha together with the nuclear localization of IFN gamma-R beta, could be a tumoral cell response, although perhaps insufficient to inhibit the uncontrolled cell proliferation. Perhaps, IFN gamma might be unable to activate p21 to stop the cell cycle, suggesting a possible participation in breast cancer development.