Related Experiment Video
Updated: May 2, 2026
Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
Published on: August 12, 2015
Glucocorticoid receptor repression mediated by BRCA1 inactivation in ovarian cancer
Yuan-Yuan Fang, Da Li1, Chen Cao
1Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang 110004, China. leeda@ymail.com.
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.
Insights
Glucocorticoid receptor (GR) levels decrease with BRCA1 repression in ovarian cancer. BRCA1 influences GR expression, suggesting GR is a potential therapeutic target for BRCA1-related ovarian cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- BRCA mutations are key hereditary factors in ovarian cancer.
- Glucocorticoid receptor (GR) is increasingly implicated in ovarian cancer development.
- The interplay between BRCA1 and GR signaling pathways remains unclear.
Purpose of the Study:
- To investigate the regulatory relationship between BRCA1 and GR in ovarian cancer.
- To determine if BRCA1 status affects GR expression levels.
- To explore the therapeutic potential of targeting GR in BRCA1-related ovarian cancer.
Main Methods:
- Assessed BRCA1 and GR expression in 146 serous ovarian cancer patients using immunohistochemistry and real-time PCR.
- Analyzed BRCA1 promoter methylation via bisulfite sequencing.
- Utilized gene knockdown and overexpression in cell lines (293 T, SKOV3) to study BRCA1-GR interactions.
Main Results:
- GR levels were unchanged in non-BRCA1/BRCA2 mutated or BRCA2-mutated ovarian cancer.
- BRCA1 repression (mutation or hypermethylation) correlated with decreased GR levels.
- Positive correlation found between BRCA1 and GR expression; BRCA1 manipulation altered GR levels in cell lines.
Conclusions:
- BRCA1 status significantly impacts GR expression in ovarian cancer.
- GR may serve as a downstream target for BRCA1 in ovarian cancer progression.
- Targeting GR could be a viable strategy for treating BRCA1-related ovarian cancers.
More Related Videos
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:20The Retinoblastoma Gene
01:31The Intrinsic Apoptotic Pathway
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:12Loss of Tumor Suppressor Gene Functions
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...