Authors: Pâmela Rossi Menegotto Patrícia Luciana da Costa Lopez Bárbara Kunzler Souza Caroline Brunetto de Farias Eduardo Cremonese FilippiChiela Igor Araújo Vieira Gilberto Schwartsmann Guido Lenz Rafael Roesler
Publish Date: 2016/01/16
Volume: 54, Issue: 2, Pages: 888-894
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 gastrinreleasing 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 therapeutic target in GBMThis research was supported by the National Council for Scientific and Technological Development CNPq grant numbers 484185/20128 and 303276/20134 to R R the National Institute for Translational Medicine INCTTM the Children’s Cancer Institute ICI the South American Office for Anticancer Drug Development and the HCPA institutional research fund FIPE/HCPA
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