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HFE variants and the expression of iron-related proteins in breast cancer-associated lymphocytes and macrophages

dc.contributor.authorMarques, Oriana
dc.contributor.authorRosa, Ana
dc.contributor.authorLeite, Luciana
dc.contributor.authorFaustino, Paula
dc.contributor.authorRêma, Alexandra
dc.contributor.authorMartins da silva, Berta
dc.contributor.authorPorto, Graça
dc.contributor.authorLopes, Carlos
dc.date.accessioned2017-02-14T13:55:02Z
dc.date.available2017-02-14T13:55:02Z
dc.date.issued2016-12-27
dc.descriptionDisponível em: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264664/pt_PT
dc.description.abstractThe association of HFE (High Iron FE) major variants with breast cancer risk and behavior has been a matter of discussion for a long time. However, their impact on the expression of iron-related proteins in the breast cancer tissue has never been addressed. In the present study, hepcidin, ferroportin 1, transferrin receptor 1 (TfR1), and ferritin expressions, as well as tissue iron deposition were evaluated in a collection of samples from breast cancers patients and analyzed according to the patients’ HFE genotype. Within the group of patients with invasive carcinoma, those carrying the p.Cys282Tyr variant in heterozygosity presented a higher expression of hepcidin in lymphocytes and macrophages than wild-type or p.His63Asp carriers. An increased expression of TfR1 was also observed in all the cell types analyzed but only in p.Cys282Tyr/p.His63Asp compound heterozygous patients. A differential impact of the two HFE variants was further noticed with the observation of a significantly higher percentage of p.Cys282Tyr heterozygous patients presenting tissue iron deposition in comparison to p.His63Asp heterozygous. In the present cohort, no significant associations were found between HFE variants and classical clinicopathological markers of breast cancer behavior and prognosis. Although limited by a low sampling size, our results provide a new possible explanation for the previously reported impact of HFE major variants on breast cancer progression, i.e., not by influencing systemic iron homeostasis but rather by differentially modulating the local cellular expression of iron-related proteins and tissue iron deposition.pt_PT
dc.description.sponsorshipOM is a recipient of the PhD grant SFRH/BD/2011/78184 from Fundação para a Ciência e Tecnologia (FCT). The authors also acknowledge financial support from ICBAS/AI&NSUMIB and by national funds through FCT and Ministério da Educação e Ciência (MEC) and when applicable co-funded by FEDER funds within the partnership agreement PT2020 related with the research unit number 4293.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCancer Microenviron. 2016 Dec;9(2-3):85-91. doi: 10.1007/s12307-016-0191-4. Epub 2016 Dec 27.pt_PT
dc.identifier.doi10.1007/s12307-016-0191-4pt_PT
dc.identifier.issn1875-2292
dc.identifier.urihttp://hdl.handle.net/10400.18/4162
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer/International Cancer Microenvironment Societypt_PT
dc.relation.publisherversionhttp://link.springer.com/article/10.1007%2Fs12307-016-0191-4pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectBreast Cancerpt_PT
dc.subjectHFEpt_PT
dc.subjectHigh Iron FEpt_PT
dc.subjectIronpt_PT
dc.subjectp.Cys282Tyrpt_PT
dc.subjectDoenças Genéticaspt_PT
dc.subjectCancropt_PT
dc.subjectMetabolismo do Ferropt_PT
dc.subjectModificadores Genéticospt_PT
dc.subjectHepcidinapt_PT
dc.titleHFE variants and the expression of iron-related proteins in breast cancer-associated lymphocytes and macrophagespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage91pt_PT
oaire.citation.startPage85pt_PT
oaire.citation.titleCancer Microenvironmentpt_PT
oaire.citation.volume9(2-3)pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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