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

<p>Abstract</p> <p>Background</p> <p>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 IFNγ induces...

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Main Authors: Paniagua Ricardo, Fraile Benito, Ruiz A Antonio, Ricote Mónica, García-Tuñón Ignacio, Royuela Mar
Format: Article
Language:English
Published: BMC 2007-08-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/7/158
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author Paniagua Ricardo
Fraile Benito
Ruiz A Antonio
Ricote Mónica
García-Tuñón Ignacio
Royuela Mar
author_facet Paniagua Ricardo
Fraile Benito
Ruiz A Antonio
Ricote Mónica
García-Tuñón Ignacio
Royuela Mar
author_sort Paniagua Ricardo
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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 IFNγ induces growth arrest at mid-G1. At the present there are no <it>in vivo </it>studies in human breast. The aim of this study was to investigate the expression patterns of IFNγ and its two receptors (IFNγ-Rα and IFNγ-Rβ) by Western blot and immunohistochemistry, in order to elucidate its role in the different types of human breast cancer (<it>in situ </it>and infiltrative).</p> <p>Methods</p> <p>Immunohistochemical and semiquantitative study of IFNγ, its receptors types (IFNγ-Rα and IFNγ-Rβ), cell proliferation (proliferating cell nuclear antigen, also named PCNA), and apoptosis (TUNEL method) was carried between the three breast groups (fibrocystic lesions, <it>in situ</it> tumors and infiltrating tumors).</p> <p>Results</p> <p>In the three groups of patients, IFNγ and IFNγ-Rα immunoreactions appeared in the cytoplasm while IFNγ-Rβ also was found in the nucleus. The optical density to IFNγ was higher in <it>in situ </it>carcinoma than in benign and infiltrating tumors. When we observed IFNγ-Rα, the optical density was lower in infiltrating carcinoma than in benign and <it>in situ </it>tumors (the higher density). To IFNγ-Rβ, 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. IFNγ 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 IFNγ, or also to an alteration of either its receptors or some transduction elements.</p> <p>Conclusion</p> <p>We conclude that the decrease in the % positive samples that expressed IFNγ and IFNγ-Rα together with the nuclear localization of IFNγ-Rβ, could be a tumoral cell response, although perhaps insufficient to inhibit the uncontrolled cell proliferation. Perhaps, IFNγ might be unable to activate p21 to stop the cell cycle, suggesting a possible participation in breast cancer development.</p>
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spelling doaj.art-e6f12f1b5049410cb215c8309ff47c1c2022-12-22T02:50:08ZengBMCBMC Cancer1471-24072007-08-017115810.1186/1471-2407-7-158Influence of IFN-gamma and its receptors in human breast cancerPaniagua RicardoFraile BenitoRuiz A AntonioRicote MónicaGarcía-Tuñón IgnacioRoyuela Mar<p>Abstract</p> <p>Background</p> <p>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 IFNγ induces growth arrest at mid-G1. At the present there are no <it>in vivo </it>studies in human breast. The aim of this study was to investigate the expression patterns of IFNγ and its two receptors (IFNγ-Rα and IFNγ-Rβ) by Western blot and immunohistochemistry, in order to elucidate its role in the different types of human breast cancer (<it>in situ </it>and infiltrative).</p> <p>Methods</p> <p>Immunohistochemical and semiquantitative study of IFNγ, its receptors types (IFNγ-Rα and IFNγ-Rβ), cell proliferation (proliferating cell nuclear antigen, also named PCNA), and apoptosis (TUNEL method) was carried between the three breast groups (fibrocystic lesions, <it>in situ</it> tumors and infiltrating tumors).</p> <p>Results</p> <p>In the three groups of patients, IFNγ and IFNγ-Rα immunoreactions appeared in the cytoplasm while IFNγ-Rβ also was found in the nucleus. The optical density to IFNγ was higher in <it>in situ </it>carcinoma than in benign and infiltrating tumors. When we observed IFNγ-Rα, the optical density was lower in infiltrating carcinoma than in benign and <it>in situ </it>tumors (the higher density). To IFNγ-Rβ, 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. IFNγ 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 IFNγ, or also to an alteration of either its receptors or some transduction elements.</p> <p>Conclusion</p> <p>We conclude that the decrease in the % positive samples that expressed IFNγ and IFNγ-Rα together with the nuclear localization of IFNγ-Rβ, could be a tumoral cell response, although perhaps insufficient to inhibit the uncontrolled cell proliferation. Perhaps, IFNγ might be unable to activate p21 to stop the cell cycle, suggesting a possible participation in breast cancer development.</p>http://www.biomedcentral.com/1471-2407/7/158
spellingShingle Paniagua Ricardo
Fraile Benito
Ruiz A Antonio
Ricote Mónica
García-Tuñón Ignacio
Royuela Mar
Influence of IFN-gamma and its receptors in human breast cancer
BMC Cancer
title Influence of IFN-gamma and its receptors in human breast cancer
title_full Influence of IFN-gamma and its receptors in human breast cancer
title_fullStr Influence of IFN-gamma and its receptors in human breast cancer
title_full_unstemmed Influence of IFN-gamma and its receptors in human breast cancer
title_short Influence of IFN-gamma and its receptors in human breast cancer
title_sort influence of ifn gamma and its receptors in human breast cancer
url http://www.biomedcentral.com/1471-2407/7/158
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AT ricotemonica influenceofifngammaanditsreceptorsinhumanbreastcancer
AT garciatunonignacio influenceofifngammaanditsreceptorsinhumanbreastcancer
AT royuelamar influenceofifngammaanditsreceptorsinhumanbreastcancer