Estudo funcional do gene mapk7, proposto como marcador prognóstico em osteosarcoma

Osteosarcomas (OS) are the most common malignant bone tumors, and the identification of useful tumor biomarkers and target proteins is required to predict the clinical outcome of patients and therapeutic response as well as to develop novel therapeutic strategies. In our previous study, MAPK7 have been identified as candidate oncogene and supposed prognostic marker for OS. Sequential activation of protein kinases within the mitogen-activated protein kinase (MAPK) cascades is a common mechanism of signal transduction in many cellular processes. In this study, we investigated the behavior of MAPK7 gene in OS cell lines. Technical viability, proliferation, migration, invasion and apoptosis were used to evaluate the function of the MAPK7 gene. We evaluated the behavior of the OS cells with MAPK7 gene silenced, not silenced and with induction of the main chemotherapy drugs used in OS treatment. We found that MAPK7 gene silenced is effective at suppressing cell proliferation, inhibiting cell migration and invasion. Furthermore, MAPK7 is an important activator of transcription factors and is the main modulates expression of other key genes from the MAPK pathway. In summary, our studies suggest that MAPK7 might be a promising therapeutic compound for OS.O osteossarcoma (OS) é o tumor ósseo maligno mais frequente com um pico de manifestação durante a segunda década de vida e é caracterizado pelo alto risco de desenvolver metástases, sendo o pulmão o sítio mais frequente.Em relação ao tratamento, nos últimos vinte anos não foram introduzidas nenhuma droga nova e os avanços na sobrevida alcançaram um platô. Dessa forma, o foco das pesquisas tem se voltado para um maior entendimento a respeito da biologia básica do OS. Décadas de estudos têm sido investidas para a melhor compreensão da genética e biologia do OS, no entanto, sua etiologia ainda é desconhecida. Em nosso estudo anterior, o gene MAPK7 foi identificado como um candidato oncogene e suposto marcador de prognóstico para o OS. Assim, neste presente estudo, investigamos a presença de mutação, inserção, deleção e/ou SNP (Single Nucleotide Polymorphism) que possa ser responsável pelo aumento de expressão do gene MAPK7 em amostras de OS, também avaliamos o comportamento do gene MAPK7 silenciado, não silenciado e com a exposição das principais drogas quimioterápicas utilizadas no tratamento OS utilizando técnicas de viabilidade, proliferação, migração, invasão e apoptose em linhagens celulares de OS. Observamos que o gene MAPK7 silenciado é eficaz na supressão da proliferação, migração e invasão celular. Além disso, MAPK7 é um ativador importante de fatores de transcrição e é o principal modulador da expressão de outros genes importantes da via MAPK. Em resumo, nossos estudos sugerem que MAPK7 pode ser um composto terapêutico promissor para o OS.Dados abertos - Sucupira - Teses e dissertações (2013 a 2016

Investigation of quantitative mRNA expression of genes located on chromosome gains regions in osteosarcom

BV UNIFESP: Teses e dissertaçõe

MAPK7 Gene Controls Proliferation, Migration and Cell Invasion in Osteosarcoma

Osteosarcomas (OS) are the most common malignant bone tumors, and the identification of useful tumor biomarkers and target proteins is required to predict the clinical outcome of patients and therapeutic response as well as to develop novel therapeutic strategies. In our previous study, MAPK7 has been identified as a candidate oncogene, and a promising prognostic marker for OS. Sequential activation of protein kinases within the mitogen-activated protein kinase (MAPK) cascades is a common mechanism of signal transduction in many cellular processes. In this study, we investigated the behavior of MAPK7 gene in OS cell lines. Technical viability, proliferation, migration, invasion, and apoptosis were used to evaluate the function of the MAPK7 gene. We evaluated the behavior of the OS cells with MAPK7 gene silenced, not silenced, and exposed to the main chemotherapy drugs used in OS treatment. We found that silenced MAPK7 gene is effective at suppressing cell proliferation, inhibiting cell migration, and invasion. Furthermore, MAPK7 is an important activator of transcription factors and is the main expression modulator of other key genes in the MAPK pathway. In summary, our study suggests that MAPK7 might be a promising therapeutic target for OS. (C) 2015 Wiley Periodicals, Inc.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Pediatric Oncology Institute IOP-GRAACC/UNIFESPUniv Fed Sao Paulo, Pediat Oncol Inst IOP GRAACC, Genet Lab, Dept Pediat, Rua Botucatu 743,8th Floor, BR-04023062 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Pediat Oncol Inst IOP GRAACC, Genet Lab, Dept Morphol & Genet, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Pediat Oncol Inst IOP GRAACC, Genet Lab, Dept Clin & Expt Oncol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Pediat Oncol Inst IOP GRAACC, Dept Pediat, Sao Paulo, SP, BrazilDepartment of Pediatrics, Genetics Laboratory, Pediatric Oncology Institute (IOP/GRAACC), Universidade Federal de São Paulo (UNIFESP), São Paulo‐SP, BrazilDepartment of Morphology and Genetics, Genetics Laboratory, Pediatric Oncology Institute (IOP/GRAACC), Universidade Federal de São Paulo (UNIFESP), São Paulo‐SP, BrazilDepartment of Clinical and Experimental Oncology, Genetics Laboratory, Pediatric Oncology Institute (IOP/GRAACC), Universidade Federal de São Paulo (UNIFESP), São Paulo‐SP, BrazilDepartment of Pediatrics, Pediatric Oncology Institute (IOP/GRAACC), Universidade Federal de São Paulo (UNIFESP), São Paulo‐SP, BrazilFAPESP: 2010/10782-8FAPESP: 2011/10459-5Web of Scienc

Insights on PRAME and osteosarcoma by means of gene expression profiling

Osteosarcoma (OS) is the most frequent bone tumor in children and adolescents. Tumor antigens are encoded by genes that are expressed in many types of solid tumors but are silent in normal tissues, with the exception of placenta and male germ-line cells. It has been proposed that antigen tumors are potential tumor markers.The premise of this study is that the identification of novel OS-associated transcripts will lead to a better understanding of the events involved in OS pathogenesis and biology.We analyzed the expression of a panel of seven tumor antigens in OS samples to identify possible tumor markers. After selecting the tumor antigen expressed in most samples of the panel, gene expression profiling was used to identify osteosarcoma-associated molecular alterations. A microarray was employed because of its ability to accurately produce comprehensive expression profiles.PRAME was identified as the tumor antigen expressed in most OS samples; it was detected in 68% of the cases. Microarray results showed differences in expression for genes functioning in cell signaling and adhesion as well as extracellular matrix-related genes, implying that such tumors could indeed differ in regard to distinct patterns of tumorigenesis.The hypothesis inferred in this study was gathered mostly from available data concerning other kinds of tumors. There is circumstantial evidence that PRAME expression might be related to distinct patterns of tumorigenesis. Further investigation is needed to validate the differential expression of genes belonging to tumorigenesis-related pathways in PRAME-positive and PRAME-negative tumors.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)GRAACC (Grupo de Apoio ao Adolescente e Crianca com Cancer)Universidade Federal de São Paulo, UNIFESP, Pediat Oncol Inst GRAACC, Dept Pediat,Genet Lab, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morphol & Genet, BR-04023062 São Paulo, BrazilUniv São Paulo, Dept Clin Med, BR-14049 Ribeirao Preto, SP, BrazilUniv São Paulo, Fac Med Ribeirao Preto, Ctr Cellbased Therapy, BR-14049 Ribeirao Preto, SP, BrazilUniv São Paulo, Dept Genet & Evolutionary Biol, BR-14049 Ribeirao Preto, SP, BrazilAlbert Einstein Res & Educ Inst, São Paulo, BrazilUniv São Paulo, Dept Genet, BR-14049 Ribeirao Preto, SP, BrazilUniv São Paulo, Dept Pediat, BR-14049 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Dept Pathol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Orthoped Surg & Traumatol, BR-04023062 São Paulo, BrazilLudwig Inst, New York, NY USAUniversidade Federal de São Paulo, UNIFESP, Pediat Oncol Inst GRAACC, Dept Pediat,Genet Lab, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morphol & Genet, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pathol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Orthoped Surg & Traumatol, BR-04023062 São Paulo, BrazilFAPESP: 04/12150-8FAPESP: 07/53869-3Web of Scienc

Insights on PRAME and osteosarcoma by means of gene expression profiling

Osteosarcoma (OS) is the most frequent bone tumor in children and adolescents. Tumor antigens are encoded by genes that are expressed in many types of solid tumors but are silent in normal tissues, with the exception of placenta and male germ-line cells. It has been proposed that antigen tumors are potential tumor markers. The premise of this study is that the identification of novel OS-associated transcripts will lead to a better understanding of the events involved in OS pathogenesis and biology. We analyzed the expression of a panel of seven tumor antigens in OS samples to identify possible tumor markers. After selecting the tumor antigen expressed in most samples of the panel, gene expression profiling was used to identify osteosarcoma-associated molecular alterations. A microarray was employed because of its ability to accurately produce comprehensive expression profiles. PRAME was identified as the tumor antigen expressed in most OS samples; it was detected in 68% of the cases. Microarray results showed differences in expression for genes functioning in cell signaling and adhesion as well as extracellular matrix-related genes, implying that such tumors could indeed differ in regard to distinct patterns of tumorigenesis. The hypothesis inferred in this study was gathered mostly from available data concerning other kinds of tumors. There is circumstantial evidence that PRAME expression might be related to distinct patterns of tumorigenesis. Further investigation is needed to validate the differential expression of genes belonging to tumorigenesis-related pathways in PRAME-positive and PRAME-negative tumors.FAPESP (The State of Sao Paulo Research Foundation)[04/12150-8]FAPESP (The State of Sao Paulo Research Foundation)[07/53869-3]GRAACC (Grupo de Apoio ao Adolescente e Crianca com Cancer