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BRCA1 and BARD1 colocalize mainly in the cytoplasm of breast cancer tumors, and their isoforms show differential expression

Authors :
Pilar Carvallo
Teresa Tapia
Cristóbal Herrera-Cares
Carolina Alvarez
Jorge L. Gamboa
Valeria Cornejo
Patricia Gajardo-Meneses
David Wiener
Wanda Fernandez
Sebastián Carvajal Díaz
Victoria Ortega-Hernández
Source :
Breast Cancer Research and Treatment. 153:669-678
Publication Year :
2015
Publisher :
Springer Science and Business Media LLC, 2015.

Abstract

BRCA1 has been found to be absent or miss localized in the cytoplasm in a relevant proportion of breast cancer tumors with no germline mutations. BRCA1 main function is in the nucleus, and its interaction with BARD1 is relevant for its nuclear translocation and retention. Our aim was to analyze the sub-cellular localization of BRCA1 and BARD1 in breast cancer tumors, and determine the level of expression of their splice variants BRCA1-Δ11q and BARD1-α and BARD1-β. BRCA1 and BARD1 expressions were performed by immunohistochemistry and immunofluorescence in 103 breast cancer tumors. Colocalization was determined by confocal microscopy. Transcript variants were determined by qRT-PCR. We found BRCA1 localized in the cytoplasm with BARD1 in 51.4 % of tumors. An exclusive nuclear localization of both proteins was observed in 7/103 tumors (6.8 %). Indeed, these tumors displayed an apparent nucleolar colocalization of BARD1 and BRCA1. In relation to splice variants, there is a tendency to an overexpression of BARD1-α mRNA (30 % of tumors) and a decreased expression of BARD1-β (41 %). BRCA1 full-length was downregulated in 63 % of tumors, and 37 % showed BRCA1-Δ11q variant overexpressed. Our findings contribute to a better understanding of the expression and sub-cellular localization of BRCA1 in breast cancer tumors. Interaction of BRCA1 and BARD1 seems to be not affected in 58.2 % of tumors, which showed colocalization of both proteins. The absence of BRCA1 in 41 % of tumors reveals a BRCAness phenotype, constituting an excellent marker for therapy sensitivity, to platinum drugs or PARP inhibitors.

Details

ISSN :
15737217 and 01676806
Volume :
153
Database :
OpenAIRE
Journal :
Breast Cancer Research and Treatment
Accession number :
edsair.doi.dedup.....dd59cebc4c4c416914da2b234774ab73
Full Text :
https://doi.org/10.1007/s10549-015-3575-0