| Autor: |
Manish Ranjan, Oukseub Lee, Gannon Cottone, Elnaz Mirzaei Mehrabad, Benjamin T. Spike, Zexian Zeng, Shivangi Yadav, Robert Chatterton, J. Julie Kim, Susan E. Clare, Seema A. Khan |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Breast Cancer Research, Vol 23, Iss 1, Pp 1-17 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
1465-542X |
| DOI: |
10.1186/s13058-021-01455-2 |
| Popis: |
Abstract Background The ovarian hormones estrogen and progesterone (EP) are implicated in breast cancer causation. A specific consequence of progesterone exposure is the expansion of the mammary stem cell (MSC) and luminal progenitor (LP) compartments. We hypothesized that this effect, and its molecular facilitators, could be abrogated by progesterone receptor (PR) antagonists administered in a mouse model. Methods Ovariectomized FVB mice were randomized to 14 days of treatment: sham, EP, EP + telapristone (EP + TPA), EP + mifepristone (EP + MFP). Mice were then sacrificed, mammary glands harvested, and mammary epithelial cell lineages separated by flow cytometry using cell surface markers. RNA from each lineage was sequenced and differential gene expression was analyzed using DESeq. Quantitative PCR was performed to confirm the candidate genes discovered in RNA seq. ANOVA with Tukey post hoc analysis was performed to compare relative expression. Alternative splicing events were examined using the rMATs multivariate analysis tool. Results Significant increases in the MSC and luminal mature (LM) cell fractions were observed following EP treatment compared to control (p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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