Schüler-Toprak Susanne, Häring Julia, Inwald Elisabeth C, Moehle Christoph, Ortmann Olaf, Treeck Oliver
Department of Gynaecology and Obstetrics, University Medical Center Regensburg, Caritas-Hospital St. Josef, Landshuter Str. 65, 93053, Regensburg, Germany.
Center of Excellence for Fluorescent Bioanalytics (KFB), Am BioPark 9, 93053, Regensburg, Germany.
BMC Cancer. 2016 Dec 21;16(1):951. doi: 10.1186/s12885-016-2973-y.
Estrogen receptor β (ERβ) is expressed in the majority of invasive breast cancer cases, irrespective of their subtype, including triple-negative breast cancer (TNBC). Thus, ERβ might be a potential target for therapy of this challenging cancer type. In this in vitro study, we examined the role of ERβ in invasion of two triple-negative breast cancer cell lines.
MDA-MB-231 and HS578T breast cancer cells were treated with the specific ERβ agonists ERB-041, WAY200070, Liquiritigenin and 3β-Adiol. Knockdown of ERβ expression was performed by means of siRNA transfection. Effects on cellular invasion were assessed in vitro by means of a modified Boyden chamber assay. Transcriptome analyses were performed using Affymetrix Human Gene 1.0 ST microarrays. Pathway and gene network analyses were performed by means of Genomatix and Ingenuity Pathway Analysis software.
Invasiveness of MBA-MB-231 and HS578T breast cancer cells decreased after treatment with ERβ agonists ERB-041 and WAY200070. Agonists Liquiritigenin and 3β-Adiol only reduced invasion of MDA-MB-231 cells. Knockdown of ERβ expression increased invasiveness of MDA-MB-231 cells about 3-fold. Transcriptome and pathway analyses revealed that ERβ knockdown led to activation of TGFβ signalling and induced expression of a network of genes with functions in extracellular matrix, tumor cell invasion and vitamin D3 metabolism.
Our data suggest that ERβ suppresses invasiveness of triple-negative breast cancer cells in vitro. Whether ERβ agonists might be useful drugs in the treatment of triple-negative breast cancer, has to be evaluated in further animal and clinical studies.
雌激素受体β（ERβ）在大多数浸润性乳腺癌病例中均有表达，无论其亚型如何，包括三阴性乳腺癌（TNBC）。因此，ERβ可能是这种具有挑战性的癌症类型的潜在治疗靶点。在这项体外研究中，我们研究了ERβ在两种三阴性乳腺癌细胞系侵袭中的作用。
用特异性ERβ激动剂ERB-041、WAY200070、甘草素和3β-雄甾二醇处理MDA-MB-231和HS578T乳腺癌细胞。通过siRNA转染敲低ERβ表达。通过改良的Boyden小室试验在体外评估对细胞侵袭的影响。使用Affymetrix Human Gene 1.0 ST微阵列进行转录组分析。通过Genomatix和Ingenuity Pathway Analysis软件进行通路和基因网络分析。
用ERβ激动剂ERB-041和WAY200070处理后，MBA-MB-231和HS578T乳腺癌细胞的侵袭性降低。激动剂甘草素和3β-雄甾二醇仅降低了MDA-MB-231细胞的侵袭。敲低ERβ表达使MDA-MB-231细胞的侵袭性增加约3倍。转录组和通路分析表明，敲低ERβ导致TGFβ信号通路激活，并诱导了一组在细胞外基质、肿瘤细胞侵袭和维生素D3代谢中具有功能的基因网络的表达。
我们的数据表明，ERβ在体外抑制三阴性乳腺癌细胞的侵袭性。ERβ激动剂是否可能成为治疗三阴性乳腺癌的有用药物，必须在进一步的动物和临床研究中进行评估。
