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Specific and redundant activities of ETV1 and ETV4 in prostate cancer aggressiveness revealed by co-overexpression cellular contexts

Genomic rearrangements involving ETS transcription factors are found in 50–70% of prostate carcinomas. While the large majority of the rearrangements involve ERG, around 10% involve members of the PEA3 subfamily (ETV1, ETV4 and ETV5). Using a panel of prostate cancer cell lines we found co-overexpre...

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Autores principales: Mesquita, Diana, Barros-Silva, João D., Santos, Joana, Skotheim, Rolf I., Lothe, Ragnhild A., Paulo, Paula, Teixeira, Manuel R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467144/
https://www.ncbi.nlm.nih.gov/pubmed/25595908
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author Mesquita, Diana
Barros-Silva, João D.
Santos, Joana
Skotheim, Rolf I.
Lothe, Ragnhild A.
Paulo, Paula
Teixeira, Manuel R.
author_facet Mesquita, Diana
Barros-Silva, João D.
Santos, Joana
Skotheim, Rolf I.
Lothe, Ragnhild A.
Paulo, Paula
Teixeira, Manuel R.
author_sort Mesquita, Diana
collection PubMed
description Genomic rearrangements involving ETS transcription factors are found in 50–70% of prostate carcinomas. While the large majority of the rearrangements involve ERG, around 10% involve members of the PEA3 subfamily (ETV1, ETV4 and ETV5). Using a panel of prostate cancer cell lines we found co-overexpression of ETV1 and ETV4 in two cell line models of advanced prostate cancer (MDA-PCa-2b and PC3) and questioned whether these PEA3 family members would cooperate in the acquisition of oncogenic properties or show functional redundancy. Using shRNAs we found that ETV1 and ETV4 have partially overlapping functions, with ETV1 being more relevant for cell invasion and ETV4 for anchorage-independent growth. In vitro expression signatures revealed the regulation of both specific and shared candidate targets that may resemble cellular mechanisms in vivo by interaction with the same intermediate partners. By combining the phenotypic impact data and the gene expression profiles of in vitro models with clinico-pathological features and gene expression profiles of ETS-subtyped tumors, we identified a set of eight genes associated with advanced stage and a set of three genes associated with higher Gleason score, supporting an oncogenic role of ETV1 and ETV4 overexpression and revealing gene sets that may be useful as prognostic markers.
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spelling pubmed-44671442015-06-22 Specific and redundant activities of ETV1 and ETV4 in prostate cancer aggressiveness revealed by co-overexpression cellular contexts Mesquita, Diana Barros-Silva, João D. Santos, Joana Skotheim, Rolf I. Lothe, Ragnhild A. Paulo, Paula Teixeira, Manuel R. Oncotarget Research Paper Genomic rearrangements involving ETS transcription factors are found in 50–70% of prostate carcinomas. While the large majority of the rearrangements involve ERG, around 10% involve members of the PEA3 subfamily (ETV1, ETV4 and ETV5). Using a panel of prostate cancer cell lines we found co-overexpression of ETV1 and ETV4 in two cell line models of advanced prostate cancer (MDA-PCa-2b and PC3) and questioned whether these PEA3 family members would cooperate in the acquisition of oncogenic properties or show functional redundancy. Using shRNAs we found that ETV1 and ETV4 have partially overlapping functions, with ETV1 being more relevant for cell invasion and ETV4 for anchorage-independent growth. In vitro expression signatures revealed the regulation of both specific and shared candidate targets that may resemble cellular mechanisms in vivo by interaction with the same intermediate partners. By combining the phenotypic impact data and the gene expression profiles of in vitro models with clinico-pathological features and gene expression profiles of ETS-subtyped tumors, we identified a set of eight genes associated with advanced stage and a set of three genes associated with higher Gleason score, supporting an oncogenic role of ETV1 and ETV4 overexpression and revealing gene sets that may be useful as prognostic markers. Impact Journals LLC 2015-02-14 /pmc/articles/PMC4467144/ /pubmed/25595908 Text en Copyright: © 2015 Mesquita et al. http://creativecommons.org/licenses/by/2.5/ 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
Mesquita, Diana
Barros-Silva, João D.
Santos, Joana
Skotheim, Rolf I.
Lothe, Ragnhild A.
Paulo, Paula
Teixeira, Manuel R.
Specific and redundant activities of ETV1 and ETV4 in prostate cancer aggressiveness revealed by co-overexpression cellular contexts
title Specific and redundant activities of ETV1 and ETV4 in prostate cancer aggressiveness revealed by co-overexpression cellular contexts
title_full Specific and redundant activities of ETV1 and ETV4 in prostate cancer aggressiveness revealed by co-overexpression cellular contexts
title_fullStr Specific and redundant activities of ETV1 and ETV4 in prostate cancer aggressiveness revealed by co-overexpression cellular contexts
title_full_unstemmed Specific and redundant activities of ETV1 and ETV4 in prostate cancer aggressiveness revealed by co-overexpression cellular contexts
title_short Specific and redundant activities of ETV1 and ETV4 in prostate cancer aggressiveness revealed by co-overexpression cellular contexts
title_sort specific and redundant activities of etv1 and etv4 in prostate cancer aggressiveness revealed by co-overexpression cellular contexts
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467144/
https://www.ncbi.nlm.nih.gov/pubmed/25595908
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