Androgen Receptor Expression in the Various Regions of Resected Glioblastoma Multiforme Tumors and in an In Vitro Model

Abstract

Glioblastoma multiforme (GBM) is a malignant glioma, difficult to detect and with the lowest survival rates among gliomas. Its greater incidence among men and its higher survival rate among premenopausal women suggest that it may be associated with the levels of androgens. As androgens stimulate the androgen receptor (AR), which acts as a transcription factor, the aim of this study was the investigate the role of AR in the progression of GBM. The study was conducted on tissues collected from three regions of GBM tumors (tumor core, enhancing tumor region, and peritumoral area). In addition, an in vitro experiment was conducted on U-87 cells under various culture conditions (necrotic, hypoxic, and nutrient-deficient), mimicking the conditions in a tumor. In both of the models, androgen receptor expression was determined at the gene and protein levels, and the results were confirmed by confocal microscopy and immunohistochemistry. AR mRNA expression was higher under nutrient-deficient conditions and lower under hypoxic conditions in vitro. However, there were no differences in AR protein expression. No differences in AR mRNA expression were observed between the tested tumor structures taken from patients. No differences in AR mRNA expression were observed between the men and women. However, AR protein expression in tumors resected from patients was higher in the enhancing tumor region and in the peritumoral area than in the tumor core. In women, higher AR expression was observed in the peritumoral area than in the tumor core. AR expression in GBM tumors did not differ significantly between men and women, which suggests that the higher incidence of GBM in men is not associated with AR expression. In the group consisting of men and women, AR expression varied between the regions of the tumor: AR expression was higher in the enhancing tumor region and in the peritumoral area than in the tumor core, showing a dependence on tumor conditions (hypoxia and insufficient nutrient supply).

Intracranial Assessment of Androgen Receptor Antagonists in Mice Bearing Human Glioblastoma Implants

“…Glioblastoma, characterized by its aggressive nature and limited treatment options, has long been a formidable challenge in the field of oncology [ 1 , 2 ]. A noteworthy development is the recognition of AR expression in a considerable percentage of glioblastoma cases, suggesting a promising avenue for potential therapeutic interventions [ 3 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ].…”

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

“…In the present study, we used a research scheme from a previously published paper: Androgen Receptor Expression in the Various Regions of Resected Glioblastoma Multiforme Tumors and in an In Vitro Model, by Simi ńska et al [69].…”

“…The in vitro model was established using a cell culture of the U87 line to test whether factors such as hypoxia, nutrient deficiency, and necrosis that affect the formation of different areas in the tumor alter the expression of estrogen receptors. A detailed description of the culture conditions is presented in Simi ńska et al [69]; this article provides a summary of the procedure.…”

“…In the second research model (a detailed description of the model is given in Simi ńska et al [69]), material taken from different areas of the patient's tumor (tumor core, enhancing tumor region, and peritumoral area) was introduced to show differences in estrogen receptor expression in different areas of the tumor.…”

“…For both research models, gene expression analysis of ESR1 and ESR2 was performed in a manner similar to the previous work [69]. In this paper, we briefly describe the research techniques used.…”