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雌激素受体 α 和 β 在不同部位切除的多形性胶质母细胞瘤肿瘤组织和体外模型中的表达。

Estrogen α and β Receptor Expression in the Various Regions of Resected Glioblastoma Multiforme Tumors and in an In Vitro Model.

机构信息

Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland.

Department of Anaesthesiology and Intensive Care, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, 71-252 Szczecin, Poland.

出版信息

Int J Mol Sci. 2024 Apr 8;25(7):4130. doi: 10.3390/ijms25074130.

Abstract

Glioblastoma multiforme (GBM) is a malignant tumor with a higher prevalence in men and a higher survival rate in transmenopausal women. It exhibits distinct areas influenced by changing environmental conditions. This study examines how these areas differ in the levels of estrogen receptors (ERs) which play an important role in the development and progression of many cancers, and whose expression levels are often correlated with patient survival. This study utilized two research models: an in vitro model employing the U87 cell line and a second model involving tumors resected from patients (including tumor core, enhancing tumor region, and peritumoral area). ER expression was assessed at both gene and protein levels, with the results validated using confocal microscopy and immunohistochemistry. Under hypoxic conditions, the U87 line displayed a decrease in ERβ mRNA expression and an increase in ERα mRNA expression. In patient samples, ERβ mRNA expression was lower in the tumor core compared to the enhancing tumor region (only in males when the study group was divided by sex). In addition, ERβ protein expression was lower in the tumor core than in the peritumoral area (only in women when the study group was divided by sex). Immunohistochemical analysis indicated the highest ERβ protein expression in the enhancing tumor area, followed by the peritumoral area, and the lowest in the tumor core. The findings suggest that ER expression may significantly influence the development of GBM, exhibiting variability under the influence of conditions present in different tumor areas.

摘要

多形性胶质母细胞瘤(GBM)是一种男性患病率较高、绝经后女性生存率较高的恶性肿瘤。它表现出明显受环境变化影响的区域。本研究探讨了这些区域在雌激素受体(ERs)水平上的差异,ERs 在许多癌症的发生和发展中起着重要作用,其表达水平通常与患者的生存相关。本研究使用了两种研究模型:体外模型采用 U87 细胞系,另一种模型涉及从患者中切除的肿瘤(包括肿瘤核心、增强肿瘤区域和肿瘤周围区域)。在基因和蛋白水平上评估 ER 表达,使用共聚焦显微镜和免疫组织化学验证结果。在缺氧条件下,U87 系中 ERβmRNA 表达下降,ERαmRNA 表达增加。在患者样本中,与增强肿瘤区域相比,肿瘤核心中的 ERβmRNA 表达较低(仅在按性别分组的研究组中男性如此)。此外,与肿瘤周围区域相比,肿瘤核心中的 ERβ 蛋白表达较低(仅在按性别分组的研究组中女性如此)。免疫组织化学分析表明,增强肿瘤区域的 ERβ 蛋白表达最高,其次是肿瘤周围区域,肿瘤核心最低。这些发现表明,ER 表达可能对 GBM 的发展有显著影响,在不同肿瘤区域存在的条件影响下表现出可变性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4359/11012502/3a5045cdf0ae/ijms-25-04130-g001.jpg

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