Epigenetic regulation of Gfi1 in endocrine-related cancers: a role regulating tumor growth

Prostate and breast cancer constitute the most common cancers among men and women worldwide. The aging population is one of the main risk factors for prostate and breast cancer development and accumulating studies link aging with epigenetic changes. Growth factor independence-1 (Gfi1) is a transcrip...

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Autores: Ashour, Nadia, Angulo, Javier C., González-Corpas, Ana, Orea, Maria J., Lobo, María V.T., Colomer Bosch, Ramón, Colás, Begoña, Esteller, Manel, 1968-, Ropero, Santiago
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/172251
Acceso en línea:https://hdl.handle.net/2445/172251
Access Level:acceso abierto
Palabra clave:Càncer de pròstata
Càncer de mama
ADN
Metilació
Prostate cancer
Breast cancer
DNA
Methylation
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spelling Epigenetic regulation of Gfi1 in endocrine-related cancers: a role regulating tumor growthAshour, NadiaAngulo, Javier C.González-Corpas, AnaOrea, Maria J.Lobo, María V.T.Colomer Bosch, RamónColás, BegoñaEsteller, Manel, 1968-Ropero, SantiagoCàncer de pròstataCàncer de mamaADNMetilacióProstate cancerBreast cancerDNAMethylationProstate and breast cancer constitute the most common cancers among men and women worldwide. The aging population is one of the main risk factors for prostate and breast cancer development and accumulating studies link aging with epigenetic changes. Growth factor independence-1 (Gfi1) is a transcriptional repressor with an important role in human malignancies, including leukemia, colorectal carcinoma, and lung cancer, but its role in prostate and breast cancer is unknown. We have found that Gfi1 epigenetic silencing is a common event in prostate and breast cancer. Gfi1 re-expression in prostate and breast cancer cell lines displaying Gfi1 epigenetic silencing decreases cell proliferation, reduced colony formation density, and tumor growth in nude mice xenografts. In addition, we found that Gfi1 repress alpha 1-anti-trypsin (AAT) and alpha 1-anti-chymotrypsin (ACT) expression, two genes with important functions in cancer development, suggesting that Gfi1 silencing promotes tumor growth by increasing AAT and ACT expression in our system. Finally, Gfi1 epigenetic silencing could be a promising biomarker for prostate cancer progression because it is associated with shorter disease-free survival. In conclusion, our findings strongly indicate that Gfi1 epigenetic silencing in prostate and breast cancer could be a crucial step in the development of these two-well characterized endocrine related tumors.MDPI2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/172251Articles publicats en revistes (Ciències Fisiològiques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3390/ijms21134687International Journal of Molecular Sciences, 2020, vol. 21, num. 13, p. 4687https://doi.org/10.3390/ijms21134687cc-by (c) Ashour, Nadia et al., 2020http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1722512026-05-27T06:46:51Z
dc.title.none.fl_str_mv Epigenetic regulation of Gfi1 in endocrine-related cancers: a role regulating tumor growth
title Epigenetic regulation of Gfi1 in endocrine-related cancers: a role regulating tumor growth
spellingShingle Epigenetic regulation of Gfi1 in endocrine-related cancers: a role regulating tumor growth
Ashour, Nadia
Càncer de pròstata
Càncer de mama
ADN
Metilació
Prostate cancer
Breast cancer
DNA
Methylation
title_short Epigenetic regulation of Gfi1 in endocrine-related cancers: a role regulating tumor growth
title_full Epigenetic regulation of Gfi1 in endocrine-related cancers: a role regulating tumor growth
title_fullStr Epigenetic regulation of Gfi1 in endocrine-related cancers: a role regulating tumor growth
title_full_unstemmed Epigenetic regulation of Gfi1 in endocrine-related cancers: a role regulating tumor growth
title_sort Epigenetic regulation of Gfi1 in endocrine-related cancers: a role regulating tumor growth
dc.creator.none.fl_str_mv Ashour, Nadia
Angulo, Javier C.
González-Corpas, Ana
Orea, Maria J.
Lobo, María V.T.
Colomer Bosch, Ramón
Colás, Begoña
Esteller, Manel, 1968-
Ropero, Santiago
author Ashour, Nadia
author_facet Ashour, Nadia
Angulo, Javier C.
González-Corpas, Ana
Orea, Maria J.
Lobo, María V.T.
Colomer Bosch, Ramón
Colás, Begoña
Esteller, Manel, 1968-
Ropero, Santiago
author_role author
author2 Angulo, Javier C.
González-Corpas, Ana
Orea, Maria J.
Lobo, María V.T.
Colomer Bosch, Ramón
Colás, Begoña
Esteller, Manel, 1968-
Ropero, Santiago
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer de pròstata
Càncer de mama
ADN
Metilació
Prostate cancer
Breast cancer
DNA
Methylation
topic Càncer de pròstata
Càncer de mama
ADN
Metilació
Prostate cancer
Breast cancer
DNA
Methylation
description Prostate and breast cancer constitute the most common cancers among men and women worldwide. The aging population is one of the main risk factors for prostate and breast cancer development and accumulating studies link aging with epigenetic changes. Growth factor independence-1 (Gfi1) is a transcriptional repressor with an important role in human malignancies, including leukemia, colorectal carcinoma, and lung cancer, but its role in prostate and breast cancer is unknown. We have found that Gfi1 epigenetic silencing is a common event in prostate and breast cancer. Gfi1 re-expression in prostate and breast cancer cell lines displaying Gfi1 epigenetic silencing decreases cell proliferation, reduced colony formation density, and tumor growth in nude mice xenografts. In addition, we found that Gfi1 repress alpha 1-anti-trypsin (AAT) and alpha 1-anti-chymotrypsin (ACT) expression, two genes with important functions in cancer development, suggesting that Gfi1 silencing promotes tumor growth by increasing AAT and ACT expression in our system. Finally, Gfi1 epigenetic silencing could be a promising biomarker for prostate cancer progression because it is associated with shorter disease-free survival. In conclusion, our findings strongly indicate that Gfi1 epigenetic silencing in prostate and breast cancer could be a crucial step in the development of these two-well characterized endocrine related tumors.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/172251
url https://hdl.handle.net/2445/172251
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/ijms21134687
International Journal of Molecular Sciences, 2020, vol. 21, num. 13, p. 4687
https://doi.org/10.3390/ijms21134687
dc.rights.none.fl_str_mv cc-by (c) Ashour, Nadia et al., 2020
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Ashour, Nadia et al., 2020
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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