Activation of β-adrenergic receptor promotes cellular proliferation in human glioblastoma.

Abstract

Glioblastoma multiforme is the most common and aggressive form of primary malignant brain tumor. Previous evidence demonstrates that β-adrenergic receptors (β-ARs) are closely associated with the occurrence and development of brain tumors. However, the functional role of β-ARs in human glioblastoma and the underlying mechanisms are not fully understood. In the present study, by using the MTT assay, western blotting, and the reverse transcription polymerase chain reaction, it was revealed that isoproterenol (ISO), an agonist of β-ARs, promoted the proliferation of U251 cells but not U87-MG cells, and that this effect was blocked by the β-ARs antagonist propranolol. It was also demonstrated that ISO transiently induced extracellular signal-related kinase 1/2 (ERK1/2) phosphorylation, and that blocking the mitogen-activated protein kinase pathway by U0126 inhibited ERK1/2 phosphorylation and suppressed U251 cell proliferation. In addition, β-ARs activation increased the expression of matrix metalloproteinase (MMP) family members MMP-2 and MMP-9 mRNA through ERK1/2 activation. In conclusion, these data suggest that β-ARs induce ERK1/2 phosphorylation, which may in turn increase MMPs expression to promote U251 cell proliferation. These results provide additional insight into the specific roles of β-ARs in glioblastoma.