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雄激素和雌激素β受体表达增强三阴性乳腺癌细胞系抗激素治疗的疗效。

Androgen and Estrogen β Receptor Expression Enhances Efficacy of Antihormonal Treatments in Triple-Negative Breast Cancer Cell Lines.

机构信息

Department Animal Physiology, Veterinary Medicine School, Complutense University of Madrid (UCM), 28040 Madrid, Spain.

Obstetrics and Gynecology Department, Hospital Clinico San Carlos, Instituto de Salud de la Mujer, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IsISSC), 28040 Madrid, Spain.

出版信息

Int J Mol Sci. 2024 Jan 25;25(3):1471. doi: 10.3390/ijms25031471.

DOI:10.3390/ijms25031471
PMID:38338747
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10855276/
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.

摘要

三阴性乳腺癌(TNBC)的特点是缺乏 ERα(雌激素受体 α)、PR(孕激素受体)的表达,HER-2 无过表达。然而,TNBC 可以表达雄激素受体(AR)或雌激素受体 β(ERβ)。此外,TNBC 分泌甾体激素,并受激素波动的影响,因此甾体抑制可能对 TNBC 的治疗产生有益的影响。本研究旨在评估使用人 TNBC 细胞系评估 dutasteride、anastrozole 和 ASP9521 在体外过程中的作用。为此,进行了免疫荧光、敏感性、增殖和伤口愈合测定,并研究了激素浓度。结果表明,所有 TNBC 细胞系均表达 AR 和 ERβ;表达最强烈的细胞系对抗激素治疗更敏感。所有治疗均降低了细胞活力,MDA-MB-453 和 SUM-159 细胞尤为明显。事实上,这些细胞系中的雄激素水平下降,这可能与细胞活力下降有关。此外,MCF-7 和 SUM-159 在治疗下增加了细胞迁移,增加了雌激素水平,这可能有利于细胞迁移。因此,抗激素治疗可能对 TNBC 治疗有益。本研究阐明了甾体激素在 AR 和 ERβ 阳性 TNBC 细胞系中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cd/10855276/9a0aad5b6ae2/ijms-25-01471-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cd/10855276/8a6bed7d049b/ijms-25-01471-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cd/10855276/da879cc66758/ijms-25-01471-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cd/10855276/170cd69d7872/ijms-25-01471-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cd/10855276/5331eb56e5a0/ijms-25-01471-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cd/10855276/9a0aad5b6ae2/ijms-25-01471-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cd/10855276/8a6bed7d049b/ijms-25-01471-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cd/10855276/da879cc66758/ijms-25-01471-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cd/10855276/170cd69d7872/ijms-25-01471-g003.jpg
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