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首页> 外文期刊>Journal of Advanced Research >Inflammatory breast cancer: Activation of the aryl hydrocarbon receptor and its target CYP1B1 correlates closely with Wnt5a/b-β-catenin signalling, the stem cell phenotype and disease progression
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Inflammatory breast cancer: Activation of the aryl hydrocarbon receptor and its target CYP1B1 correlates closely with Wnt5a/b-β-catenin signalling, the stem cell phenotype and disease progression

机译：炎性乳腺癌：芳烃受体及其靶标CYP1B1的激活与Wnt5a /b-β-catenin信号传导，干细胞表型和疾病进展密切相关

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The aim of the present study was to evaluate the expression levels of the aryl hydrocarbon receptor (AHR) and its target gene CYP1B1 and to correlate their expression with Wnt5a/b-β-catenin, the CD44sup+/sup/CD24sup(?/low)/sup cancer stem cell (CSC) subset and factors associated with poor prognosis in inflammatory breast cancer (IBC) and non-IBC patients. The methods of analysis used were quantitative real-time PCR, western blotting, immunohistochemistry and flow cytometry. Compared to non-IBC tissues, IBC tissues exhibited the overexpression of AHR and its target gene/protein CYP1B1. AHR and CYP1B1 mRNA levels were associated with the poor clinical prognosis markers tumour grade, lymphovascular invasion, cell proliferation and lymph node metastasis. Furthermore, AHR expression correlated with the expression of Wnt5a/b and β-catenin signalling molecules, and Wnt5a mRNA expression was downregulated in the SUM149 human IBC cell line and the MDA-MB-231 non-IBC cell line upon inhibition of AHR. AHR gene knockout (CRISPR-Cas9) inhibits CYP1B1 and Wnt5a expression in the IBC cell line. The CD44sup+/sup/CD24sup(?/low)/sup subset was significantly correlated with the expression of AHR, CYP1B1, Wnt5a/b and β-catenin in IBC tissues. The overexpression of AHR and its target CYP1B1 correlated with the expression of Wnt5a/b and β-catenin, CSCs, and poor clinical prognostic factors of IBC. Thus, targeting AHR and/or its downstream target molecules CYP1B1 and Wnt5a/b may represent a therapeutic approach for IBC.
机译：本研究的目的是评估芳烃受体（AHR）及其靶基因CYP1B1的表达水平，并将其与Wnt5a /b-β-catenin，CD44 + /相关联CD24 （？/ low）癌症干细胞（CSC）子集以及与炎症性乳腺癌（IBC）和非IBC患者的不良预后相关的因素。所使用的分析方法为实时荧光定量PCR，蛋白质印迹，免疫组织化学和流式细胞仪。与非IBC组织相比，IBC组织表现出AHR及其靶基因/蛋白质CYP1B1的过表达。 AHR和CYP1B1 mRNA水平与不良的临床预后标志物肿瘤等级，淋巴血管浸润，细胞增殖和淋巴结转移有关。此外，AHR表达与Wnt5a / b和β-连环蛋白信号分子的表达相关，并且在抑制AHR后，SUM149人IBC细胞系和MDA-MB-231非IBC细胞系中的Wnt5a mRNA表达下调。 AHR基因敲除（CRISPR-Cas9）抑制CYP1B1和Wnt5a在IBC细胞系中的表达。 CD44 + / CD24 （？/ low）子集与IBC组织中AHR，CYP1B1，Wnt5a / b和β-catenin的表达显着相关。 AHR及其靶标CYP1B1的过表达与Wnt5a / b和β-catenin，CSCs的表达以及IBC的临床预后不良有关。因此，靶向AHR和/或其下游靶分子CYP1B1和Wnt5a / b可能代表IBC的治疗方法。

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