Livin/BIRC7 expression as malignancy marker in adrenocortical tumors

Livin/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumor development through the inhibition of caspases. Aim was to investigate the expression of livin and other members of its pathway in adrenocortical tumors and in the adrenocortical carcinoma (ACC) cell...

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Autores principales: Altieri, Barbara, Sbiera, Silviu, Casa, Silvia Della, Weigand, Isabel, Wild, Vanessa, Steinhauer, Sonja, Fadda, Guido, Kocot, Arkadius, Bekteshi, Michaela, Mambretti, Egle M, Rosenwald, Andreas, Pontecorvi, Alfredo, Fassnacht, Martin, Ronchi, Cristina L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354734/
https://www.ncbi.nlm.nih.gov/pubmed/28030838
http://dx.doi.org/10.18632/oncotarget.14067
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author Altieri, Barbara
Sbiera, Silviu
Casa, Silvia Della
Weigand, Isabel
Wild, Vanessa
Steinhauer, Sonja
Fadda, Guido
Kocot, Arkadius
Bekteshi, Michaela
Mambretti, Egle M
Rosenwald, Andreas
Pontecorvi, Alfredo
Fassnacht, Martin
Ronchi, Cristina L
author_facet Altieri, Barbara
Sbiera, Silviu
Casa, Silvia Della
Weigand, Isabel
Wild, Vanessa
Steinhauer, Sonja
Fadda, Guido
Kocot, Arkadius
Bekteshi, Michaela
Mambretti, Egle M
Rosenwald, Andreas
Pontecorvi, Alfredo
Fassnacht, Martin
Ronchi, Cristina L
author_sort Altieri, Barbara
collection PubMed
description Livin/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumor development through the inhibition of caspases. Aim was to investigate the expression of livin and other members of its pathway in adrenocortical tumors and in the adrenocortical carcinoma (ACC) cell line NCI-H295R. The mRNA expression of livin, its isoforms α and β, XIAP, CASP3 and DIABLO was evaluated by qRT-PCR in 82 fresh-frozen adrenal tissues (34 ACC, 25 adenomas = ACA, 23 normal adrenal glands = NAG). Livin protein expression was assessed by immunohistochemistry in 270 paraffin-embedded tissues (192 ACC, 58 ACA, 20 NAG). Livin, CASP3 and cleaved caspase-3 were evaluated in NCI-H295R after induction of livin overexpression. Relative livin mRNA expression was significantly higher in ACC than in ACA and NAG (0.060 ± 0.116 vs 0.004 ± 0.014 and 0.002 ± 0.009, respectively, p < 0.01), being consistently higher in tumors than in adjacent NAG and isoform β more expressed than α. No significant differences in CASP3, XIAP and DIABLO levels were found among these groups. In immunohistochemistry, livin was localized in both cytoplasm and nuclei. The ratio between cytoplasmic and nuclear staining was significantly higher in ACC (1.51 ± 0.66) than in ACA (0.80 ± 0.35) and NAG (0.88 ± 0.27; p < 0.0001). No significant correlations were observed between livin expression and histopathological parameters or clinical outcome. In NCI-H295R cells, the livin overexpression slightly reduced the activation of CASP3, but did not correlate with cell viability. In conclusion, livin is specifically over-expressed in ACC, suggesting that it might be involved in adrenocortical tumorigenesis and represent a new molecular marker of malignancy.
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spelling pubmed-53547342017-04-14 Livin/BIRC7 expression as malignancy marker in adrenocortical tumors Altieri, Barbara Sbiera, Silviu Casa, Silvia Della Weigand, Isabel Wild, Vanessa Steinhauer, Sonja Fadda, Guido Kocot, Arkadius Bekteshi, Michaela Mambretti, Egle M Rosenwald, Andreas Pontecorvi, Alfredo Fassnacht, Martin Ronchi, Cristina L Oncotarget Research Paper Livin/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumor development through the inhibition of caspases. Aim was to investigate the expression of livin and other members of its pathway in adrenocortical tumors and in the adrenocortical carcinoma (ACC) cell line NCI-H295R. The mRNA expression of livin, its isoforms α and β, XIAP, CASP3 and DIABLO was evaluated by qRT-PCR in 82 fresh-frozen adrenal tissues (34 ACC, 25 adenomas = ACA, 23 normal adrenal glands = NAG). Livin protein expression was assessed by immunohistochemistry in 270 paraffin-embedded tissues (192 ACC, 58 ACA, 20 NAG). Livin, CASP3 and cleaved caspase-3 were evaluated in NCI-H295R after induction of livin overexpression. Relative livin mRNA expression was significantly higher in ACC than in ACA and NAG (0.060 ± 0.116 vs 0.004 ± 0.014 and 0.002 ± 0.009, respectively, p < 0.01), being consistently higher in tumors than in adjacent NAG and isoform β more expressed than α. No significant differences in CASP3, XIAP and DIABLO levels were found among these groups. In immunohistochemistry, livin was localized in both cytoplasm and nuclei. The ratio between cytoplasmic and nuclear staining was significantly higher in ACC (1.51 ± 0.66) than in ACA (0.80 ± 0.35) and NAG (0.88 ± 0.27; p < 0.0001). No significant correlations were observed between livin expression and histopathological parameters or clinical outcome. In NCI-H295R cells, the livin overexpression slightly reduced the activation of CASP3, but did not correlate with cell viability. In conclusion, livin is specifically over-expressed in ACC, suggesting that it might be involved in adrenocortical tumorigenesis and represent a new molecular marker of malignancy. Impact Journals LLC 2016-12-21 /pmc/articles/PMC5354734/ /pubmed/28030838 http://dx.doi.org/10.18632/oncotarget.14067 Text en Copyright: © 2017 Altieri et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Altieri, Barbara
Sbiera, Silviu
Casa, Silvia Della
Weigand, Isabel
Wild, Vanessa
Steinhauer, Sonja
Fadda, Guido
Kocot, Arkadius
Bekteshi, Michaela
Mambretti, Egle M
Rosenwald, Andreas
Pontecorvi, Alfredo
Fassnacht, Martin
Ronchi, Cristina L
Livin/BIRC7 expression as malignancy marker in adrenocortical tumors
title Livin/BIRC7 expression as malignancy marker in adrenocortical tumors
title_full Livin/BIRC7 expression as malignancy marker in adrenocortical tumors
title_fullStr Livin/BIRC7 expression as malignancy marker in adrenocortical tumors
title_full_unstemmed Livin/BIRC7 expression as malignancy marker in adrenocortical tumors
title_short Livin/BIRC7 expression as malignancy marker in adrenocortical tumors
title_sort livin/birc7 expression as malignancy marker in adrenocortical tumors
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354734/
https://www.ncbi.nlm.nih.gov/pubmed/28030838
http://dx.doi.org/10.18632/oncotarget.14067
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