Abstract | INTRODUCTION: MATERIALS AND METHODS: Since MDA-MB-453 triple-negative breast cancer cells express mutated AR, PTEN, and p53, MDA-MB-231 triple-negative breast cancer cells stably expressing wildtype AR (MDA-MB-231-AR) were used to evaluate the in vitro and in vivo anti-proliferative effects of SARMs. Microarray analysis and epithelial:mesenchymal stem cell (MSC) co-culture signaling studies were performed to understand the mechanisms of action. RESULTS:
Dihydrotestosterone and SARMs, but not bicalutamide, inhibited the proliferation of MDA-MB-231-AR. The SARMs reduced the MDA-MB-231-AR tumor growth and tumor weight by greater than 90%, compared to vehicle-treated tumors. SARM treatment inhibited the intratumoral expression of genes and pathways that promote breast cancer development through its actions on the AR. SARM treatment also inhibited the metastasis-promoting paracrine factors, IL6 and MMP13, and subsequent migration and invasion of epithelial:MSC co-cultures. CONCLUSION:
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Authors | Ramesh Narayanan, Sunjoo Ahn, Misty D Cheney, Muralimohan Yepuru, Duane D Miller, Mitchell S Steiner, James T Dalton |
Journal | PloS one
(PLoS One)
Vol. 9
Issue 7
Pg. e103202
( 2014)
ISSN: 1932-6203 [Electronic] United States |
PMID | 25072326
(Publication Type: Journal Article)
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Chemical References |
- Receptors, Androgen
- Selective Estrogen Receptor Modulators
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Topics |
- Animals
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Disease Models, Animal
- Female
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- Mesenchymal Stem Cells
(drug effects, metabolism)
- Mice
- Mice, Nude
- Neoplasm Metastasis
- Paracrine Communication
(drug effects)
- Receptors, Androgen
(metabolism)
- Selective Estrogen Receptor Modulators
(pharmacology)
- Signal Transduction
(drug effects)
- Triple Negative Breast Neoplasms
(genetics, metabolism, pathology)
- Tumor Burden
(drug effects)
- Xenograft Model Antitumor Assays
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