关键词: estrogen receptor α estrogen receptor β glioblastoma multiforme hypoxia nuclear sex hormone receptors nutrient deficiency

Mesh : Male Humans Female Glioblastoma / genetics Estrogen Receptor beta / genetics Gene Expression Estrogens RNA, Messenger / genetics

来  源:   DOI:10.3390/ijms25074130   PDF(Pubmed)

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)是一种恶性肿瘤,在男性中患病率较高,在绝经妇女中生存率较高。它表现出受环境条件变化影响的不同区域。这项研究探讨了这些区域在雌激素受体(ER)水平上的差异,雌激素受体在许多癌症的发展和进展中起着重要作用。其表达水平通常与患者生存相关。这项研究利用了两种研究模型:一种是采用U87细胞系的体外模型,另一种是涉及从患者身上切除的肿瘤(包括肿瘤核心,增强肿瘤区域,和肿瘤周围区域)。在基因和蛋白质水平上评估ER表达,结果验证使用共聚焦显微镜和免疫组织化学。在缺氧条件下,U87品系显示ERβmRNA表达减少,ERαmRNA表达增加。在病人样本中,与肿瘤增强区域相比,肿瘤核心中的ERβmRNA表达较低(仅在男性中,研究组按性别划分)。此外,肿瘤核心的ERβ蛋白表达低于肿瘤周围区域(仅在研究组按性别划分的女性中)。免疫组织化学分析显示增强肿瘤区ERβ蛋白表达最高,其次是肿瘤周围区域,和最低的肿瘤核心。提示ER的表达可能显著影响GBM的发生发展,在不同肿瘤区域存在的条件的影响下表现出变异性。
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