Impaired OXPHOS complex III in breast cancer.

We measured the mitochondrial oxidative phosphorylation (mtOXPHOS) activities of all five complexes and determined the activity and gene expression in detail of the Complex III subunits in human breast cancer cell lines and primary tumors. Our analysis revealed dramatic differences in activity of co...

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Main Authors: Kjerstin M Owens, Mariola Kulawiec, Mohamad Mokhtar Desouki, Ayyasamy Vanniarajan, Keshav K Singh
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3162009?pdf=render
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author Kjerstin M Owens
Mariola Kulawiec
Mohamad Mokhtar Desouki
Ayyasamy Vanniarajan
Keshav K Singh
author_facet Kjerstin M Owens
Mariola Kulawiec
Mohamad Mokhtar Desouki
Ayyasamy Vanniarajan
Keshav K Singh
author_sort Kjerstin M Owens
collection DOAJ
description We measured the mitochondrial oxidative phosphorylation (mtOXPHOS) activities of all five complexes and determined the activity and gene expression in detail of the Complex III subunits in human breast cancer cell lines and primary tumors. Our analysis revealed dramatic differences in activity of complex III between normal and aggressive metastatic breast cancer cell lines. Determination of Complex III subunit gene expression identified over expression and co-regulation of UQCRFS1 (encoding RISP protein) and UQCRH (encoding Hinge protein) in 6 out of 9 human breast tumors. Analyses of UQCRFS1/RISP expression in additional matched normal and breast tumors demonstrated an over expression in 14 out of 40 (35%) breast tumors. UQCRFS1/RISP knockdown in breast tumor cell line led to decreased mitochondrial membrane potential as well as a decrease in matrigel invasion. Furthermore, reduced matrigel invasion was mediated by reduced ROS levels coinciding with decreased expression of NADPH oxidase 2, 3, 4 and 5 involved in ROS production. These studies provide direct evidence for contribution of impaired mtOXPHOS Complex III to breast tumorigenesis.
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spelling doaj.art-71b1cac57c5c465b9a40acaebcd737e52022-12-21T18:32:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2384610.1371/journal.pone.0023846Impaired OXPHOS complex III in breast cancer.Kjerstin M OwensMariola KulawiecMohamad Mokhtar DesoukiAyyasamy VanniarajanKeshav K SinghWe measured the mitochondrial oxidative phosphorylation (mtOXPHOS) activities of all five complexes and determined the activity and gene expression in detail of the Complex III subunits in human breast cancer cell lines and primary tumors. Our analysis revealed dramatic differences in activity of complex III between normal and aggressive metastatic breast cancer cell lines. Determination of Complex III subunit gene expression identified over expression and co-regulation of UQCRFS1 (encoding RISP protein) and UQCRH (encoding Hinge protein) in 6 out of 9 human breast tumors. Analyses of UQCRFS1/RISP expression in additional matched normal and breast tumors demonstrated an over expression in 14 out of 40 (35%) breast tumors. UQCRFS1/RISP knockdown in breast tumor cell line led to decreased mitochondrial membrane potential as well as a decrease in matrigel invasion. Furthermore, reduced matrigel invasion was mediated by reduced ROS levels coinciding with decreased expression of NADPH oxidase 2, 3, 4 and 5 involved in ROS production. These studies provide direct evidence for contribution of impaired mtOXPHOS Complex III to breast tumorigenesis.http://europepmc.org/articles/PMC3162009?pdf=render
spellingShingle Kjerstin M Owens
Mariola Kulawiec
Mohamad Mokhtar Desouki
Ayyasamy Vanniarajan
Keshav K Singh
Impaired OXPHOS complex III in breast cancer.
PLoS ONE
title Impaired OXPHOS complex III in breast cancer.
title_full Impaired OXPHOS complex III in breast cancer.
title_fullStr Impaired OXPHOS complex III in breast cancer.
title_full_unstemmed Impaired OXPHOS complex III in breast cancer.
title_short Impaired OXPHOS complex III in breast cancer.
title_sort impaired oxphos complex iii in breast cancer
url http://europepmc.org/articles/PMC3162009?pdf=render
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AT ayyasamyvanniarajan impairedoxphoscomplexiiiinbreastcancer
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