Related Experiment Video
Updated: Jul 19, 2026
08:53
Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1
Published on: February 17, 2011
BRCA1 dysfunction in sporadic basal-like breast cancer.
N C Turner1, J S Reis-Filho, A M Russell
1Chester Beatty Laboratories, The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
Oncogene
|October 4, 2006
Summary
BRCA1 dysfunction is common in basal-like breast cancers, with reduced BRCA1 expression and increased ID4 levels. This dysfunction, particularly prevalent in metaplastic breast cancers, offers potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Basal-like breast cancer is a distinct subtype characterized by basal/myoepithelial cell markers.
- Germline BRCA1 mutations are frequently observed in basal-like breast cancers, suggesting BRCA1's role in sporadic cases.
- Understanding BRCA1 dysfunction in basal-like breast cancer is crucial for targeted therapies.
Purpose of the Study:
- To investigate the prevalence and mechanisms of BRCA1 downregulation in sporadic basal-like breast cancers.
- To explore the correlation between BRCA1 downregulation and basal markers.
- To assess BRCA1 methylation in metaplastic breast cancers.
Main Methods:
- Analysis of 37 sporadic basal-like breast cancers and matched controls for BRCA1 downregulation.
- Assessment of BRCA1 promoter methylation and BRCA1 messenger RNA (mRNA) expression.
- Quantification of ID4 expression as a potential regulator of BRCA1.
- Evaluation of BRCA1 methylation in metaplastic breast cancers.
Main Results:
- BRCA1 mRNA expression was twofold lower in basal-like breast cancers compared to controls (P=0.008).
- ID4, a negative regulator of BRCA1, was significantly upregulated (9.1-fold) in basal-like breast cancer (P<0.0001).
- BRCA1 downregulation correlated with multiple basal markers, indicating phenotypic heterogeneity.
- 63% of metaplastic breast cancers exhibited BRCA1 methylation, significantly higher than controls (P<0.0001).
Conclusions:
- BRCA1 dysfunction is prevalent in sporadic basal-like breast cancers, mediated by reduced mRNA expression and potentially regulated by ID4.
- The high frequency of BRCA1 dysfunction, especially in metaplastic subtypes, presents a potential therapeutic vulnerability.
- Targeted treatment strategies exploiting BRCA1 dysfunction could benefit patients with basal-like breast cancer.
More Related Videos
09:24Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
Published on: August 12, 2015
08:15gDNA Enrichment by a Transposase-based Technology for NGS Analysis of the Whole Sequence of BRCA1, BRCA2, and 9 Genes Involved in DNA Damage Repair
Published on: October 6, 2014
Related Concept Videos
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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,...
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,...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
02:21Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
01:12Loss of Tumor Suppressor Gene Functions
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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...
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
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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...
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...
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...