Transcription factors involved in prostate gland adaptation to androgen deprivation
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Publication Date: | 2014 |
Other Authors: | , , , , |
Format: | Article |
Source: | Repositório da Produção Científica e Intelectual da Unicamp |
Download full: | https://hdl.handle.net/20.500.12733/1665559 |
Summary: | Abstract: Androgens regulate prostate physiology, and exert their effects through the androgen receptor. We hypothesized that androgen deprivation needs additional transcription factors to orchestrate the changes taking place in the gland after castration and for the adaptation of the epithelial cells to the androgen-deprived environment, ultimately contributing to the origin of castration-resistant prostate cancer. This study was undertaken to identify transcription factors that regulate gene expression after androgen deprivation by castration (Cas). For the sake of comparison, we extended the analysis to the effects of administration of a high dose of 17 beta-estradiol (E2) and a combination of both (Cas+ E2). We approached this by (i) identifying gene expression profiles and enrichment terms, and by searching for transcription factors in the derived regulatory pathways; and (ii) by determining the density of putative transcription factor binding sites in the proximal promoter of the 10 most up- or down-regulated genes in each experimental group in comparison to the controls Gapdh and Tbp7. Filtering and validation confirmed the expression and localized EVI1 (Mecom), NFY, ELK1, GATA2, MYBL1, MYBL2, and NFkB family members (NFkB1, NFkB2, REL, RELA and RELB) in the epithelial and/or stromal cells. These transcription factors represent major regulators of epithelial cell survival and immaturity as well as an adaptation of the gland as an immune barrier in the absence of functional stimulation by androgens. Elk1 was expressed in smooth muscle cells and was up-regulated after day 4. Evi1 and Nfy genes are expressed in both epithelium and stroma, but were apparently not affected by androgen deprivation |
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Transcription factors involved in prostate gland adaptation to androgen deprivationNeoplasias da próstataProstatic neoplasmsAndrógenosAndrogensEstradiolEstradiolArtigo originalAbstract: Androgens regulate prostate physiology, and exert their effects through the androgen receptor. We hypothesized that androgen deprivation needs additional transcription factors to orchestrate the changes taking place in the gland after castration and for the adaptation of the epithelial cells to the androgen-deprived environment, ultimately contributing to the origin of castration-resistant prostate cancer. This study was undertaken to identify transcription factors that regulate gene expression after androgen deprivation by castration (Cas). For the sake of comparison, we extended the analysis to the effects of administration of a high dose of 17 beta-estradiol (E2) and a combination of both (Cas+ E2). We approached this by (i) identifying gene expression profiles and enrichment terms, and by searching for transcription factors in the derived regulatory pathways; and (ii) by determining the density of putative transcription factor binding sites in the proximal promoter of the 10 most up- or down-regulated genes in each experimental group in comparison to the controls Gapdh and Tbp7. Filtering and validation confirmed the expression and localized EVI1 (Mecom), NFY, ELK1, GATA2, MYBL1, MYBL2, and NFkB family members (NFkB1, NFkB2, REL, RELA and RELB) in the epithelial and/or stromal cells. These transcription factors represent major regulators of epithelial cell survival and immaturity as well as an adaptation of the gland as an immune barrier in the absence of functional stimulation by androgens. Elk1 was expressed in smooth muscle cells and was up-regulated after day 4. Evi1 and Nfy genes are expressed in both epithelium and stroma, but were apparently not affected by androgen deprivationFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQAbertoUNIVERSIDADE ESTADUAL DE CAMPINASRosa-Ribeiro, Rafaela, 1987-Nishan, Umar, 1985-Barbosa, Guilherme Oliveira, 1988-Reis, Leonardo Oliveira, 1978-César, Carlos Lenz, 1955-Carvalho, Hernandes Faustino de, 1965-2014info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.12733/1665559ROSA-RIBEIRO, Rafaela et al. Transcription factors involved in prostate gland adaptation to androgen deprivation. Plos one. San Francisco, CA : Public Library of Science , 2014. Vol. 9, n. 6 (June, 2014), n. art. e97080, p. 1-13. Disponível em: https://hdl.handle.net/20.500.12733/1665559. Acesso em: 24 mai. 2023.Inglêshttps://repositorio.unicamp.br/acervo/detalhe/1217382reponame:Repositório da Produção Científica e Intelectual da Unicampinstname:Universidade Estadual de Campinas (UNICAMP)instacron:UNICAMPinfo:eu-repo/semantics/openAccess2022-08-02T13:06:07Zoai:https://www.repositorio.unicamp.br/:1217382Repositório InstitucionalPUBhttp://repositorio.unicamp.br/oai/requestreposip@unicamp.bropendoar:2022-08-02T13:06:07Repositório da Produção Científica e Intelectual da Unicamp - Universidade Estadual de Campinas (UNICAMP)false |
dc.title.none.fl_str_mv |
Transcription factors involved in prostate gland adaptation to androgen deprivation |
title |
Transcription factors involved in prostate gland adaptation to androgen deprivation |
spellingShingle |
Transcription factors involved in prostate gland adaptation to androgen deprivation Rosa-Ribeiro, Rafaela, 1987- Neoplasias da próstata Prostatic neoplasms Andrógenos Androgens Estradiol Estradiol Artigo original |
title_short |
Transcription factors involved in prostate gland adaptation to androgen deprivation |
title_full |
Transcription factors involved in prostate gland adaptation to androgen deprivation |
title_fullStr |
Transcription factors involved in prostate gland adaptation to androgen deprivation |
title_full_unstemmed |
Transcription factors involved in prostate gland adaptation to androgen deprivation |
title_sort |
Transcription factors involved in prostate gland adaptation to androgen deprivation |
author |
Rosa-Ribeiro, Rafaela, 1987- |
author_facet |
Rosa-Ribeiro, Rafaela, 1987- Nishan, Umar, 1985- Barbosa, Guilherme Oliveira, 1988- Reis, Leonardo Oliveira, 1978- César, Carlos Lenz, 1955- Carvalho, Hernandes Faustino de, 1965- |
author_role |
author |
author2 |
Nishan, Umar, 1985- Barbosa, Guilherme Oliveira, 1988- Reis, Leonardo Oliveira, 1978- César, Carlos Lenz, 1955- Carvalho, Hernandes Faustino de, 1965- |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
UNIVERSIDADE ESTADUAL DE CAMPINAS |
dc.contributor.author.fl_str_mv |
Rosa-Ribeiro, Rafaela, 1987- Nishan, Umar, 1985- Barbosa, Guilherme Oliveira, 1988- Reis, Leonardo Oliveira, 1978- César, Carlos Lenz, 1955- Carvalho, Hernandes Faustino de, 1965- |
dc.subject.por.fl_str_mv |
Neoplasias da próstata Prostatic neoplasms Andrógenos Androgens Estradiol Estradiol Artigo original |
topic |
Neoplasias da próstata Prostatic neoplasms Andrógenos Androgens Estradiol Estradiol Artigo original |
description |
Abstract: Androgens regulate prostate physiology, and exert their effects through the androgen receptor. We hypothesized that androgen deprivation needs additional transcription factors to orchestrate the changes taking place in the gland after castration and for the adaptation of the epithelial cells to the androgen-deprived environment, ultimately contributing to the origin of castration-resistant prostate cancer. This study was undertaken to identify transcription factors that regulate gene expression after androgen deprivation by castration (Cas). For the sake of comparison, we extended the analysis to the effects of administration of a high dose of 17 beta-estradiol (E2) and a combination of both (Cas+ E2). We approached this by (i) identifying gene expression profiles and enrichment terms, and by searching for transcription factors in the derived regulatory pathways; and (ii) by determining the density of putative transcription factor binding sites in the proximal promoter of the 10 most up- or down-regulated genes in each experimental group in comparison to the controls Gapdh and Tbp7. Filtering and validation confirmed the expression and localized EVI1 (Mecom), NFY, ELK1, GATA2, MYBL1, MYBL2, and NFkB family members (NFkB1, NFkB2, REL, RELA and RELB) in the epithelial and/or stromal cells. These transcription factors represent major regulators of epithelial cell survival and immaturity as well as an adaptation of the gland as an immune barrier in the absence of functional stimulation by androgens. Elk1 was expressed in smooth muscle cells and was up-regulated after day 4. Evi1 and Nfy genes are expressed in both epithelium and stroma, but were apparently not affected by androgen deprivation |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/20.500.12733/1665559 ROSA-RIBEIRO, Rafaela et al. Transcription factors involved in prostate gland adaptation to androgen deprivation. Plos one. San Francisco, CA : Public Library of Science , 2014. Vol. 9, n. 6 (June, 2014), n. art. e97080, p. 1-13. Disponível em: https://hdl.handle.net/20.500.12733/1665559. Acesso em: 24 mai. 2023. |
url |
https://hdl.handle.net/20.500.12733/1665559 |
identifier_str_mv |
ROSA-RIBEIRO, Rafaela et al. Transcription factors involved in prostate gland adaptation to androgen deprivation. Plos one. San Francisco, CA : Public Library of Science , 2014. Vol. 9, n. 6 (June, 2014), n. art. e97080, p. 1-13. Disponível em: https://hdl.handle.net/20.500.12733/1665559. Acesso em: 24 mai. 2023. |
dc.language.iso.fl_str_mv |
Inglês |
language_invalid_str_mv |
Inglês |
dc.relation.none.fl_str_mv |
https://repositorio.unicamp.br/acervo/detalhe/1217382 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
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Repositório da Produção Científica e Intelectual da Unicamp |
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Repositório da Produção Científica e Intelectual da Unicamp |
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Repositório da Produção Científica e Intelectual da Unicamp - Universidade Estadual de Campinas (UNICAMP) |
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reposip@unicamp.br |
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