Testosterone Promotes Glioblastoma Cell Proliferation, Migration, and Invasion Through Androgen Receptor Activation.

Dulce Carolina Rodríguez-Lozano,Ana Gabriela Piña-Medina,Ignacio Camacho-Arroyo,Claudia Bello-Alvarez,Valeria Hansberg-Pastor

doi:10.3389/fendo.2019.00016

Abstract

Glioblastomas (GBM) are the most frequent and aggressive human brain tumors due to their high capacity to migrate and invade normal brain tissue. Epidemiological data report that GBM occur in a greater proportion in men than in women (3:2), suggesting the participation of sex hormones in the development of these tumors. It has been reported an increase in testosterone (T) levels in patients with GBM. In addition, androgen receptor (AR) is overexpressed in human GBM, and genetic silencing of AR, and its pharmacological inhibition, induce GBM cell death in vivo and in vitro. However, the role of T in proliferation, migration and invasion in human GBM cell lines has not been evaluated. We observed that T increased the number of U87, U251, and D54 cells derived from human GBM due to an increase in cell proliferation. This induction was blocked with flutamide, an antagonist of AR. T also induced migration and invasion of GBM cells that flutamide partially blocked. These data suggest that T through AR contributes to the progression of GBM by promoting proliferation, migration, and invasion.

Highlights

Glioblastomas (GBM) or grade IV astrocytomas are the most aggressive and frequent tumors in the Central Nervous System (CNS)
To determine whether human GBM cell number is modified by T, we evaluated U87, U251, and D54 cells growth rate through a time course experiment with T at different concentrations (1, 10, 100 nM and 1 μM)
We observed a significant increase in the number of cells treated with T 100 nM in the three GBM cell lines from 72 h (D54), and 96 h (U87 and U251) of treatment

Summary

Introduction

Glioblastomas (GBM) or grade IV astrocytomas are the most aggressive and frequent tumors in the Central Nervous System (CNS). They arise from uncontrolled proliferation of astrocytes, precursor glial cells, and cancer stem cells, and they are generally located in the brain cortex, basal ganglia and thalamus [1]. Androgens are involved in the regulation of Testosterone Promotes Gliblastoma Progression pathological processes such as tumor growth [10, 11]. They can exert their multiple effects through the interaction with its intracellular receptor (AR), a transcription factor that once activated, binds to specific DNA sequences called androgen response elements located in gene promoter regions, regulating their expression [12, 13]

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