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Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors
We have previously reported hepcidin and ferritin increases in the plasma of breast cancer patients, but not in patients with benign breast disease. We hypothesized that these differences in systemic iron homeostasis may reflect alterations in different iron-related proteins also play a key biochemi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343944/ https://www.ncbi.nlm.nih.gov/pubmed/28216608 http://dx.doi.org/10.3390/ijms18020410 |
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author | Pizzamiglio, Sara De Bortoli, Maida Taverna, Elena Signore, Michele Veneroni, Silvia Chi-shing Cho, William Orlandi, Rosaria Verderio, Paolo Bongarzone, Italia |
author_facet | Pizzamiglio, Sara De Bortoli, Maida Taverna, Elena Signore, Michele Veneroni, Silvia Chi-shing Cho, William Orlandi, Rosaria Verderio, Paolo Bongarzone, Italia |
author_sort | Pizzamiglio, Sara |
collection | PubMed |
description | We have previously reported hepcidin and ferritin increases in the plasma of breast cancer patients, but not in patients with benign breast disease. We hypothesized that these differences in systemic iron homeostasis may reflect alterations in different iron-related proteins also play a key biochemical and regulatory role in breast cancer. Thus, here we explored the expression of a bundle of molecules involved in both iron homeostasis and tumorigenesis in tissue samples. Enzyme-linked immunosorbent assay (ELISA) or reverse-phase protein array (RPPA), were used to measure the expression of 20 proteins linked to iron processes in 24 non-cancerous, and 56 cancerous, breast tumors. We found that cancerous tissues had higher level of hepcidin than benign lesions (p = 0.012). The univariate analysis of RPPA data highlighted the following seven proteins differentially expressed between non-cancerous and cancerous breast tissue: signal transducer and transcriptional activator 5 (STAT5), signal transducer and activator of transcription 3 (STAT3), bone morphogenetic protein 6 (BMP6), cluster of differentiation 74 (CD74), transferrin receptor (TFRC), inhibin alpha (INHA), and STAT5_pY694. These findings were confirmed for STAT5, STAT3, BMP6, CD74 and INHA when adjusting for age. The multivariate statistical analysis indicated an iron-related 10-protein panel effective in separating non-cancerous from cancerous lesions including STAT5, STAT5_pY694, myeloid differentiation factor 88 (MYD88), CD74, iron exporter ferroportin (FPN), high mobility group box 1 (HMGB1), STAT3_pS727, TFRC, ferritin heavy chain (FTH), and ferritin light chain (FTL). Our results showed an association between some iron-related proteins and the type of tumor tissue, which may provide insight in strategies for using iron chelators to treat breast cancer. |
format | Online Article Text |
id | pubmed-5343944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-53439442017-03-16 Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors Pizzamiglio, Sara De Bortoli, Maida Taverna, Elena Signore, Michele Veneroni, Silvia Chi-shing Cho, William Orlandi, Rosaria Verderio, Paolo Bongarzone, Italia Int J Mol Sci Article We have previously reported hepcidin and ferritin increases in the plasma of breast cancer patients, but not in patients with benign breast disease. We hypothesized that these differences in systemic iron homeostasis may reflect alterations in different iron-related proteins also play a key biochemical and regulatory role in breast cancer. Thus, here we explored the expression of a bundle of molecules involved in both iron homeostasis and tumorigenesis in tissue samples. Enzyme-linked immunosorbent assay (ELISA) or reverse-phase protein array (RPPA), were used to measure the expression of 20 proteins linked to iron processes in 24 non-cancerous, and 56 cancerous, breast tumors. We found that cancerous tissues had higher level of hepcidin than benign lesions (p = 0.012). The univariate analysis of RPPA data highlighted the following seven proteins differentially expressed between non-cancerous and cancerous breast tissue: signal transducer and transcriptional activator 5 (STAT5), signal transducer and activator of transcription 3 (STAT3), bone morphogenetic protein 6 (BMP6), cluster of differentiation 74 (CD74), transferrin receptor (TFRC), inhibin alpha (INHA), and STAT5_pY694. These findings were confirmed for STAT5, STAT3, BMP6, CD74 and INHA when adjusting for age. The multivariate statistical analysis indicated an iron-related 10-protein panel effective in separating non-cancerous from cancerous lesions including STAT5, STAT5_pY694, myeloid differentiation factor 88 (MYD88), CD74, iron exporter ferroportin (FPN), high mobility group box 1 (HMGB1), STAT3_pS727, TFRC, ferritin heavy chain (FTH), and ferritin light chain (FTL). Our results showed an association between some iron-related proteins and the type of tumor tissue, which may provide insight in strategies for using iron chelators to treat breast cancer. MDPI 2017-02-14 /pmc/articles/PMC5343944/ /pubmed/28216608 http://dx.doi.org/10.3390/ijms18020410 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Pizzamiglio, Sara De Bortoli, Maida Taverna, Elena Signore, Michele Veneroni, Silvia Chi-shing Cho, William Orlandi, Rosaria Verderio, Paolo Bongarzone, Italia Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors |
title | Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors |
title_full | Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors |
title_fullStr | Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors |
title_full_unstemmed | Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors |
title_short | Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors |
title_sort | expression of iron-related proteins differentiate non-cancerous and cancerous breast tumors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343944/ https://www.ncbi.nlm.nih.gov/pubmed/28216608 http://dx.doi.org/10.3390/ijms18020410 |
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