Gastrin-Releasing Peptide Receptor Knockdown Induces Senescence in Glioblastoma Cells

Molecular Neurobiology
Pâmela Rossi MenegottoRafael Roesler

Abstract

Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor, characterized by excessive cell proliferation, resistance to apoptosis, and invasiveness. Due to resistance to currently available treatment options, the prognosis for patients with GBM is very dismal. The activation of gastrin-releasing peptide receptors (GRPR) stimulates GBM cell proliferation, whereas GRPR antagonists induce antiproliferative effects in in vitro and in vivo experimental models of GBM. However, the role of GRPR in regulating other aspects of GBM cell function related to tumor progression remains poorly understood, and previous studies have not used RNA interference techniques as tools to examine GRPR function in GBM. Here, we found that stable GRPR knockdown by a lentiviral vector using a short hairpin interfering RNA sequence in human A172 GBM cells resulted in increased cell size and altered cell cycle dynamics consistent with cell senescence. These changes were accompanied by increases in the content of p53, p21, and p16, activation of epidermal growth factor receptors (EGFR), and a reduction in p38 content. These results increase our understanding of GRPR regulation of GBM cells and further support that GRPR may be a relevant therap...Continue Reading

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Citations

Nov 11, 2016·Molecular Neurobiology·Viviane Rösner AlmeidaRafael Roesler
Nov 10, 2017·Current Opinion in Endocrinology, Diabetes, and Obesity·Xiangping QuRujiao Liu
Sep 4, 2019·European Journal of Nuclear Medicine and Molecular Imaging·Lucia BarattoAndrei Iagaru
Jan 25, 2020·Biochimica Et Biophysica Acta. General Subjects·Jin Wook HwangAli G Turhan
Sep 4, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Banendu Sunder DashJyh-Ping Chen

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Methods Mentioned

BETA
surgical resection
transfection
protein assay
flow cytometry

Software Mentioned

FlowJo
ImageQuant
Image Pro Plus
ImageJ

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