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Glucocorticoid receptor repression mediated by BRCA1 inactivation in ovarian cancer

BACKGROUND: BRCA mutations are the main known hereditary factor for ovarian cancer. Notably, emerging evidence indicates that the glucocorticoid receptor (GR) has drawn considerable interest in ovarian cancer development. However, dynamic cross-talk between BRCA1 and GR signaling pathways are poorly...

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Autores principales: Fang, Yuan-Yuan, Li, Da, Cao, Chen, Li, Chun-Yan, Li, Ting-Ting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004164/
https://www.ncbi.nlm.nih.gov/pubmed/24629067
http://dx.doi.org/10.1186/1471-2407-14-188
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author Fang, Yuan-Yuan
Li, Da
Cao, Chen
Li, Chun-Yan
Li, Ting-Ting
author_facet Fang, Yuan-Yuan
Li, Da
Cao, Chen
Li, Chun-Yan
Li, Ting-Ting
author_sort Fang, Yuan-Yuan
collection PubMed
description BACKGROUND: BRCA mutations are the main known hereditary factor for ovarian cancer. Notably, emerging evidence indicates that the glucocorticoid receptor (GR) has drawn considerable interest in ovarian cancer development. However, dynamic cross-talk between BRCA1 and GR signaling pathways are poorly understood. METHODS: The regulatory effects of BRCA on GR were assessed in 146 serous ovarian cancer patients (28 pairs of BRCA1-mutated or not, 23 pairs of BRCA2-mutated or not, and 22 pairs with hypermethylated BRCA1 promoter or not). BRCA1 promoter methylation was analyzed by bisulfite sequencing using primers flanking the core promoter region. Expression levels of BRCA1 and GR were assessed by immunohistochemistry and real-time PCR. Regression analysis was used to examine the possible relationship between BRCA1 and GR expression levels. The knockdown and overexpression of BRCA1 were achieved using a lentiviral vector in 293 T cells, SKOV3 ovarian cancer cells, and primary non-mutated and BRCA1-mutated ovarian cancer cells. RESULTS: GR expression levels were unchanged in non-BRCA1-mutated, non-BRCA2-mutated and BRCA2-mutated ovarian cancer compared to their normal tissues; BRCA1 repression (BRCA1 mutation or BRCA1 promoter hypermethylation) ovarian cancer showed decreased GR levels compared to normal tissue; there was a positive correlation between BRCA1 and GR expression in human ovarian cancer specimens; BRCA1 knockdown was effective at inhibiting GR expression, and overexpression of BRCA1 induces an increase in GR levels in ovarian cancer cells. CONCLUSIONS: These results suggest that GR may be a potential target for BRCA1 in ovarian cancer progression.
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spelling pubmed-40041642014-04-30 Glucocorticoid receptor repression mediated by BRCA1 inactivation in ovarian cancer Fang, Yuan-Yuan Li, Da Cao, Chen Li, Chun-Yan Li, Ting-Ting BMC Cancer Research Article BACKGROUND: BRCA mutations are the main known hereditary factor for ovarian cancer. Notably, emerging evidence indicates that the glucocorticoid receptor (GR) has drawn considerable interest in ovarian cancer development. However, dynamic cross-talk between BRCA1 and GR signaling pathways are poorly understood. METHODS: The regulatory effects of BRCA on GR were assessed in 146 serous ovarian cancer patients (28 pairs of BRCA1-mutated or not, 23 pairs of BRCA2-mutated or not, and 22 pairs with hypermethylated BRCA1 promoter or not). BRCA1 promoter methylation was analyzed by bisulfite sequencing using primers flanking the core promoter region. Expression levels of BRCA1 and GR were assessed by immunohistochemistry and real-time PCR. Regression analysis was used to examine the possible relationship between BRCA1 and GR expression levels. The knockdown and overexpression of BRCA1 were achieved using a lentiviral vector in 293 T cells, SKOV3 ovarian cancer cells, and primary non-mutated and BRCA1-mutated ovarian cancer cells. RESULTS: GR expression levels were unchanged in non-BRCA1-mutated, non-BRCA2-mutated and BRCA2-mutated ovarian cancer compared to their normal tissues; BRCA1 repression (BRCA1 mutation or BRCA1 promoter hypermethylation) ovarian cancer showed decreased GR levels compared to normal tissue; there was a positive correlation between BRCA1 and GR expression in human ovarian cancer specimens; BRCA1 knockdown was effective at inhibiting GR expression, and overexpression of BRCA1 induces an increase in GR levels in ovarian cancer cells. CONCLUSIONS: These results suggest that GR may be a potential target for BRCA1 in ovarian cancer progression. BioMed Central 2014-03-14 /pmc/articles/PMC4004164/ /pubmed/24629067 http://dx.doi.org/10.1186/1471-2407-14-188 Text en Copyright © 2014 Fang et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Fang, Yuan-Yuan
Li, Da
Cao, Chen
Li, Chun-Yan
Li, Ting-Ting
Glucocorticoid receptor repression mediated by BRCA1 inactivation in ovarian cancer
title Glucocorticoid receptor repression mediated by BRCA1 inactivation in ovarian cancer
title_full Glucocorticoid receptor repression mediated by BRCA1 inactivation in ovarian cancer
title_fullStr Glucocorticoid receptor repression mediated by BRCA1 inactivation in ovarian cancer
title_full_unstemmed Glucocorticoid receptor repression mediated by BRCA1 inactivation in ovarian cancer
title_short Glucocorticoid receptor repression mediated by BRCA1 inactivation in ovarian cancer
title_sort glucocorticoid receptor repression mediated by brca1 inactivation in ovarian cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004164/
https://www.ncbi.nlm.nih.gov/pubmed/24629067
http://dx.doi.org/10.1186/1471-2407-14-188
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