Estrogen (E2) is crucial for the development of breast cancer caused by BRCA1 mutation, and can increase the DNA damage in BRCA1-deficient cells. However, the mechanisms through which BRCA1 deficiency and E2 synergistically induce DNA damage remains unclear. In this study, we analyzed the distribution of DNA damage in E2-treated BRCA1-deficient cells. We detected DNA lesions in the vicinity of genes that are transcriptionally activated by estrogen receptor-α (ER). Loss of BRCA1 altered chromatin binding by ER, which significantly affected the distribution of DNA damage. Moreover, these changes were associated with the established mutations in BRCA1-mutant breast cancer. Taken together, our findings reveal a new mechanism underlying the DNA damage in breast cancer cells that is synergistically induced by BRCA1 deficiency and E2.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2022.04.142 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cytotoxicity and genotoxicity of orthodontic bands after aging: an in-vitro study.
BMC Oral Health
January 2025
Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, P.O. Box 71345-3119, Shiraz, Iran.
Background: This investigation sought to evaluate cytotoxic and genotoxic effects of two different types of orthodontic bands after aging in acidic and neutral artificial saliva using human gingival fibroblast-like (HGF1-PI 1) cell lines.
Methods: Two commercial brands of orthodontic molar bands (American orthodontic (AO) and 3 S-dental bands), commonly used by orthodontists, were tested. These bands were divided into four groups to examine the effects of aging following thermocycling, and pH variations (pH = 4.
Identifying Safeguards Disabled by Epstein-Barr Virus Infections in Genomes From Patients With Breast Cancer: Chromosomal Bioinformatics Analysis.
JMIRx Med
January 2025
Department of Biochemistry and Medical Genetics, Cancer Center, University of Illinois Chicago, 900 s Ashland, Chicago, IL, 60617, United States, 1 8479124216.
Background: The causes of breast cancer are poorly understood. A potential risk factor is Epstein-Barr virus (EBV), a lifelong infection nearly everyone acquires. EBV-transformed human mammary cells accelerate breast cancer when transplanted into immunosuppressed mice, but the virus can disappear as malignant cells reproduce.
View Article and Find Full Text PDFPARP4 deficiency enhances sensitivity to ATM inhibitor by impairing DNA damage repair in melanoma.
Cell Death Discov
January 2025
Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
Besides the important pathogenic mechanisms of melanoma, including BRAF-driven and immunosuppressive microenvironment, genomic instability and abnormal DNA double-strand breaks (DSB) repair are significant driving forces for its occurrence and development. This suggests investigating novel therapeutic strategies from the synthetic lethality perspective. Poly (ADP-ribose) polymerase 4 (PARP4) is known to be a member of the PARP protein family.
View Article and Find Full Text PDFDNA-Dependent Protein Kinase Inhibitor Peposertib Enhances Efficacy of Lu-Based Radioimmunotherapy in Preclinical Models of Prostate and Renal Cell Carcinoma.
J Nucl Med
January 2025
Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia;
Novel radiation sensitizers, including inhibitors targeting DNA damage response, have been developed to enhance the efficacy of anticancer treatments that induce DNA damage in cancer cells. Peposertib, a potent, selective, and orally administered inhibitor of DNA-dependent protein kinase, impedes the nonhomologous end-joining mechanism for DNA double-strand break (DSB) repair. We investigated radioimmunotherapy alone or with peposertib in preclinical models of renal cell carcinoma (RCC) or prostate cancer.
View Article and Find Full Text PDFNucleolin-targeted silicon-based nanoparticles for enhanced chemo-sonodynamic therapy of diffuse large B-cell lymphoma.
Int J Pharm
January 2025
Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361005, China. Electronic address:
The limited selectivity and high systemic toxicity of traditional chemotherapy hinder its efficacy in treating diffuse large B-cell lymphoma (DLBCL). The combination of sonodynamic therapy (SDT) with chemotherapy has emerged as a novel strategy for cancer treatment, aiming to improve therapeutic outcomes and reduce systemic toxicity. However, challenges such as elevated drug clearance rates and non-selecitivity remain to be resolved.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!