Androgen and Estrogen β Receptor Expression Enhances Efficacy of Antihormonal Treatments in Triple-Negative Breast Cancer Cell Lines
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2024
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Crespo, B., Illera, J. C., Silvan, G., Lopez-Plaza, P., Herrera de la Muela, M., de la Puente Yagüe, M., Diaz Del Arco, C., Illera, M. J., & Caceres, S. (2024). Androgen and Estrogen β Receptor Expression Enhances Efficacy of Antihormonal Treatments in Triple-Negative Breast Cancer Cell Lines. International journal of molecular sciences, 25(3), 1471. https://doi.org/10.3390/ijms25031471
Abstract
The triple-negative breast cancer (TNBC) subtype is characterized by the lack of expression of ERα (estrogen receptor α), PR (progesterone receptor) and no overexpression of HER-2. However, TNBC can express the androgen receptor (AR) or estrogen receptor β (ERβ). Also, TNBC secretes steroid hormones and is influenced by hormonal fluctuations, so the steroid inhibition could exert a beneficial effect in TNBC treatment. The aim of this study was to evaluate the effect of dutasteride, anastrozole and ASP9521 in in vitro processes using human TNBC cell lines. For this, immunofluorescence, sensitivity, proliferation and wound healing assays were performed, and hormone concentrations were studied. Results revealed that all TNBC cell lines expressed AR and ERβ; the ones that expressed them most intensely were more sensitive to antihormonal treatments. All treatments reduced cell viability, highlighting MDA-MB-453 and SUM-159. Indeed, a decrease in androgen levels was observed in these cell lines, which could relate to a reduction in cell viability. In addition, MCF-7 and SUM-159 increased cell migration under treatments, increasing estrogen levels, which could favor cell migration. Thus, antihormonal treatments could be beneficial for TNBC therapies. This study clarifies the importance of steroid hormones in AR and ERβ-positive cell lines of TNBC.
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Author Contributions
Conceptualization, B.C., S.C., P.L.-P., M.H.d.l.M., M.d.l.P.Y., C.D.d.A. and J.C.I.; methodology, B.C., J.C.I., G.S., P.L.-P., M.H.d.l.M., M.d.l.P.Y., C.D.d.A., M.J.I. and S.C.; investigation, B.C., S.C., P.L.-P., M.H.d.l.M., M.d.l.P.Y., C.D.d.A. and J.C.I.; writing—original draft preparation, B.C., S.C. and J.C.I.; writing—review and editing, B.C., S.C., G.S., M.J.I. and J.C.I. All authors have read and agreed to the published version of the manuscript.