Caracterização da atividade da HJURP na redução do estresse replicativo de linhagens de glioblastoma
Carregando...
Data
2018-10-31
Autores
Fernandes, Barbara Colatto [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
O câncer é um conjunto de alterações celulares que favorecem a proliferação descontrolada e a aquisição de propriedades metastáticas. A ativação de oncogenes e/ou a perda de genes supressores tumorais leva a desbalanços nos mecanismos de controle do ciclo celular e/ou na inativação das vias apoptóticas, contribuindo para a instabilidade genômica presente em todos os tipos tumorais. Relatos na literatura têm sugerido que o estresse replicativo oriundo desse aumento proliferativo exacerbado é um fator importante na formação e progressão de muitos tipos de câncer. Dentro dessa perspectiva, é plausível pensar que as células tumorais tenham desenvolvido certas competências que as permitam lidar com o estresse replicativo para continuar se propagando. Resultados prévios de nosso laboratório sugerem que a proteína centromérica HJURP (Holliday Junction Recognizing Protein) esteja envolvida nesse ganho de competência. Dessa forma, esse trabalho teve como objetivo a análise do papel dessa proteína frente ao estresse replicativo em linhagens de glioblastoma. Nossos resultados demonstraram que a superexpressão de HJURP confere um aumento na capacidade proliferativa celular da linhagem U87MG. Além disso, vimos que em baixas concentrações de camptotecina as células superexpressoras de HJURP possuíam um comportamento proliferativo muito semelhante à condição não tratada. Os ensaios de citotoxicidade revelaram uma maior capacidade de recuperação frente ao estresse replicativo exógeno nas situações em que HJURP estava superexpressa. Conjuntamente, esses dados sugerem que o incremento nos níveis celulares de HJURP parece conferir uma maior resistência ao estresse replicativo induzido por camptotecina nas células U87MG.
Cancer is characterized by a subset of features that supports uncontrolled cell proliferation and acquisition of metastatic properties. Oncogene activation and/ or the deactivation of tumor suppressor genes lead to disbalances in cell cycle control progression and/or inactivation of apoptotic pathways, followed by genomic instability present in all types of tumors. According to the literature, replicative DNA stress arising from uncontrolled cell growth is the major driver in the development and progression of many cancers. In this perspective, it is believed that cancer cells have developed some skills in order to deal with high levels of endogenous replicative stress for their continued proliferation. Previous results from our group suggest that the centromeric protein HJURP (Holliday Junction Recognizing Protein) is involved in this mechanism. Thus, in this work, we aimed to analyze the role of this protein in the cellular response to the replicative stress in glioblastoma U87MG cell line. Our data showed that cells who levels of HJURP were high, had an increase in cell growth. Besides that, we also observed that at lower camptothecin concentrations the curve proliferation of overexpressed HJURP cells had a similar behavior as the control cells. The cytotoxicity results demonstrated that cells overexpressing HJURP had a better replicative induced stress when compared to the control cells. Together, this data suggests that high levels of HJURP might be responsible for resistence camptothecin-induced replicative stress in U87MG cell line.
Cancer is characterized by a subset of features that supports uncontrolled cell proliferation and acquisition of metastatic properties. Oncogene activation and/ or the deactivation of tumor suppressor genes lead to disbalances in cell cycle control progression and/or inactivation of apoptotic pathways, followed by genomic instability present in all types of tumors. According to the literature, replicative DNA stress arising from uncontrolled cell growth is the major driver in the development and progression of many cancers. In this perspective, it is believed that cancer cells have developed some skills in order to deal with high levels of endogenous replicative stress for their continued proliferation. Previous results from our group suggest that the centromeric protein HJURP (Holliday Junction Recognizing Protein) is involved in this mechanism. Thus, in this work, we aimed to analyze the role of this protein in the cellular response to the replicative stress in glioblastoma U87MG cell line. Our data showed that cells who levels of HJURP were high, had an increase in cell growth. Besides that, we also observed that at lower camptothecin concentrations the curve proliferation of overexpressed HJURP cells had a similar behavior as the control cells. The cytotoxicity results demonstrated that cells overexpressing HJURP had a better replicative induced stress when compared to the control cells. Together, this data suggests that high levels of HJURP might be responsible for resistence camptothecin-induced replicative stress in U87MG cell line.
Descrição
Palavras-chave
glioblastoma, camptotecina, HJURP, camptothecin