التفاصيل البيبلوغرافية
| العنوان: |
R-loop functions in Brca1-associated mammary tumorigenesis. |
| المؤلفون: |
Huai-Chin Chiang, Leilei Qi, Payal Mitra, Yimeng Huang, Yanfen Hu, Rong Li |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 8/13/2024, Vol. 121 Issue 33, p1-8, 17p |
| مستخلص: |
Deleterious accumulation of R-loops, a DNA-RNA hybrid structure, contributes to genome instability. They are associated with BRCA1 mutation-related breast cancer, an estrogen receptor α negative (ERα-) tumor type originating from luminal progenitor cells. However, a presumed causality of R-loops in tumorigenesis has not been established in vivo. Here, we overexpress mouse Rnaseh1 (Rh1-OE) in vivo to remove accumulated R-loops in Brca1-deficient mouse mammary epithelium (BKO). R-loop removal exacerbates DNA replication stress in proliferating BKO mammary epithelial cells, with little effect on homology-directed repair of double-strand breaks following ionizing radiation. Compared to their BKO counterparts, BKO-Rh1-OE mammary glands contain fewer luminal progenitor cells but more mature luminal cells. Despite a similar incidence of spontaneous mammary tumors in BKO and BKO-Rh1-OE mice, a significant percentage of BKO-Rh1-OE tumors express ERα and progesterone receptor. Our results suggest that rather than directly elevating the overall tumor incidence, R-loops influence the mammary tumor subtype by shaping the cell of origin for Brca1 tumors. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
