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Estrogen and BRCA1 deficiency synergistically induce breast cancer mutation-related DNA damage.
- Source :
-
Biochemical & Biophysical Research Communications . Jul2022, Vol. 613, p140-145. 6p. - Publication Year :
- 2022
-
Abstract
- 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. [Display omitted] • BRCA1 deficiency increased ER binding on specific genome region where tends to occur DNA damage. • DNA damages accumulate at the genes transcriptionally activated by ER. • DNA damage synergistically induced by BRCA1 deficiency and E2 is associated with clinical mutations. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DNA damage
*BRCA genes
*BREAST cancer
*ESTROGEN
*ETIOLOGY of cancer
*CANCER cells
Subjects
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 613
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 157119031
- Full Text :
- https://doi.org/10.1016/j.bbrc.2022.04.142