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Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling

Ovarian cancer (OC) is the most lethal gynecologic cancer characterized by an elevated apoptosis resistance that, potentially, leads to chemo-resistance in the recurrent disease. Mitochondrial oxidative phosphorylation was found altered in OC, and mitochondria were proposed as a target for therapy....

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Autores principales: Signorile, Anna, De Rasmo, Domenico, Cormio, Antonella, Musicco, Clara, Rossi, Roberta, Fortarezza, Francesco, Palese, Luigi Leonardo, Loizzi, Vera, Resta, Leonardo, Scillitani, Giovanni, Cicinelli, Ettore, Simonetti, Francesca, Ferretta, Anna, Russo, Silvia, Tufaro, Antonio, Cormio, Gennaro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770021/
https://www.ncbi.nlm.nih.gov/pubmed/31547300
http://dx.doi.org/10.3390/cancers11091350
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author Signorile, Anna
De Rasmo, Domenico
Cormio, Antonella
Musicco, Clara
Rossi, Roberta
Fortarezza, Francesco
Palese, Luigi Leonardo
Loizzi, Vera
Resta, Leonardo
Scillitani, Giovanni
Cicinelli, Ettore
Simonetti, Francesca
Ferretta, Anna
Russo, Silvia
Tufaro, Antonio
Cormio, Gennaro
author_facet Signorile, Anna
De Rasmo, Domenico
Cormio, Antonella
Musicco, Clara
Rossi, Roberta
Fortarezza, Francesco
Palese, Luigi Leonardo
Loizzi, Vera
Resta, Leonardo
Scillitani, Giovanni
Cicinelli, Ettore
Simonetti, Francesca
Ferretta, Anna
Russo, Silvia
Tufaro, Antonio
Cormio, Gennaro
author_sort Signorile, Anna
collection PubMed
description Ovarian cancer (OC) is the most lethal gynecologic cancer characterized by an elevated apoptosis resistance that, potentially, leads to chemo-resistance in the recurrent disease. Mitochondrial oxidative phosphorylation was found altered in OC, and mitochondria were proposed as a target for therapy. Molecular evidence suggests that the deregulation of mitochondrial biogenesis, morphology, dynamics, and apoptosis is involved in carcinogenesis. However, these mitochondrial processes remain to be investigated in OC. Eighteen controls and 16 OC tissues (serous and mucinous) were collected. Enzymatic activities were performed spectrophotometrically, mitochondrial DNA (mtDNA) content was measured by real-time-PCR, protein levels were determined by Western blotting, and mitochondrial number and structure were measured by electron microscopy. Statistical analysis was performed using Student’s t-test, Mann-Whitney U test, and principal component analysis (PCA). We found, in OC, that increased mitochondrial number associated with increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and mitochondrial transcription factor A (TFAM) protein levels, as well as mtDNA content. The OC mitochondria presented an increased maximum length, as well as reduced cristae width and junction diameter, associated with increased optic atrophy 1 protein (OPA1) and prohibitin 2 (PHB2) protein levels. In addition, in OC tissues, augmented cAMP and sirtuin 3 (SIRT3) protein levels were observed. PCA of the 25 analyzed biochemical parameters classified OC patients in a distinct group from controls. We highlight a “mitochondrial signature” in OC that could result from cooperation of the cAMP pathway with the SIRT3, OPA1, and PHB2 proteins.
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spelling pubmed-67700212019-10-30 Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling Signorile, Anna De Rasmo, Domenico Cormio, Antonella Musicco, Clara Rossi, Roberta Fortarezza, Francesco Palese, Luigi Leonardo Loizzi, Vera Resta, Leonardo Scillitani, Giovanni Cicinelli, Ettore Simonetti, Francesca Ferretta, Anna Russo, Silvia Tufaro, Antonio Cormio, Gennaro Cancers (Basel) Article Ovarian cancer (OC) is the most lethal gynecologic cancer characterized by an elevated apoptosis resistance that, potentially, leads to chemo-resistance in the recurrent disease. Mitochondrial oxidative phosphorylation was found altered in OC, and mitochondria were proposed as a target for therapy. Molecular evidence suggests that the deregulation of mitochondrial biogenesis, morphology, dynamics, and apoptosis is involved in carcinogenesis. However, these mitochondrial processes remain to be investigated in OC. Eighteen controls and 16 OC tissues (serous and mucinous) were collected. Enzymatic activities were performed spectrophotometrically, mitochondrial DNA (mtDNA) content was measured by real-time-PCR, protein levels were determined by Western blotting, and mitochondrial number and structure were measured by electron microscopy. Statistical analysis was performed using Student’s t-test, Mann-Whitney U test, and principal component analysis (PCA). We found, in OC, that increased mitochondrial number associated with increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and mitochondrial transcription factor A (TFAM) protein levels, as well as mtDNA content. The OC mitochondria presented an increased maximum length, as well as reduced cristae width and junction diameter, associated with increased optic atrophy 1 protein (OPA1) and prohibitin 2 (PHB2) protein levels. In addition, in OC tissues, augmented cAMP and sirtuin 3 (SIRT3) protein levels were observed. PCA of the 25 analyzed biochemical parameters classified OC patients in a distinct group from controls. We highlight a “mitochondrial signature” in OC that could result from cooperation of the cAMP pathway with the SIRT3, OPA1, and PHB2 proteins. MDPI 2019-09-12 /pmc/articles/PMC6770021/ /pubmed/31547300 http://dx.doi.org/10.3390/cancers11091350 Text en © 2019 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
Signorile, Anna
De Rasmo, Domenico
Cormio, Antonella
Musicco, Clara
Rossi, Roberta
Fortarezza, Francesco
Palese, Luigi Leonardo
Loizzi, Vera
Resta, Leonardo
Scillitani, Giovanni
Cicinelli, Ettore
Simonetti, Francesca
Ferretta, Anna
Russo, Silvia
Tufaro, Antonio
Cormio, Gennaro
Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling
title Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling
title_full Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling
title_fullStr Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling
title_full_unstemmed Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling
title_short Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling
title_sort human ovarian cancer tissue exhibits increase of mitochondrial biogenesis and cristae remodeling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770021/
https://www.ncbi.nlm.nih.gov/pubmed/31547300
http://dx.doi.org/10.3390/cancers11091350
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