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Oncotarget ; 7(48): 79572-79583, 2016 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-27788487

RESUMO

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in humans and is characterized with poor outcome. In this study, we investigated components of prolactin (Prl) system in cell models of GBM and in histological tissue sections obtained from GBM patients. Expression of Prolactin receptor (PrlR) was detected at high levels in U251-MG, at low levels in U87-MG and barely detectable in U373 cell lines and in 66% of brain tumor tissues from 32 GBM patients by immunohistochemical technique. In addition, stimulation of U251-MG and U87-MG cells but not U373 with Prl resulted in increased STAT5 phosphorylation and only in U251-MG cells with increased cellular invasion. Furthermore, STAT5 phosphorylation and cellular invasion induced in Prl stimulated cells were significantly reduced by using a Prl receptor antagonist that consists of Prl with four amino acid replacements. We conclude that Prl receptor is expressed at different levels in the majority of GBM tumors and that blocking of PrlR in U251-MG cells significantly reduce cellular invasion.


Assuntos
Neoplasias Encefálicas/metabolismo , Movimento Celular/efeitos dos fármacos , Glioblastoma/metabolismo , Prolactina/farmacologia , Receptores da Prolactina/agonistas , Fator de Transcrição STAT5/metabolismo , Antineoplásicos Hormonais/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Antagonistas de Hormônios/farmacologia , Humanos , Invasividade Neoplásica , Fosforilação , Receptores da Prolactina/antagonistas & inibidores , Receptores da Prolactina/metabolismo , Transdução de Sinais/efeitos dos fármacos
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