Differential expression of genes encoding proteins of the HGF/MET system in insulinomas

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art_MURAT_Differential_expression_of_genes_encoding_proteins_of_the_2015.PDF (1.24 MB)
Citações na Scopus
6
Tipo de produção
article
Data de publicação
2015
Editora
BIOMED CENTRAL LTD
DOI
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Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
MURAT, Cahue de Bernardis
CORREA, Luciana
GIANNELLA-NETO, Daniel
Autor de Grupo de pesquisa
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Organizadores
Citação
DIABETOLOGY & METABOLIC SYNDROME, v.7, article ID 84, 5p, 2015
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background: Insulinomas are the most common functional pancreatic neuroendocrine tumors, whereas histopathological features do not predict their biological behaviour. In an attempt to better understand the molecular processes involved in the tumorigenesis of islet beta cells, the present study evaluated the expression of genes belonging to the hepatocyte growth factor and its receptor (HGF/MET) system, namely, MET, HGF; HGFAC and ST14 (encode HGF activator and matriptase, respectively, two serine proteases that catalyze conversion of pro-HGF to active HGF); and SPINT1 and SPINT2 (encode serine peptidase inhibitors Kunitz type 1 and type 2, respectively, two inhibitors of HGF activator and of matriptase). Methods: Quantitative real-time reverse transcriptase polymerase chain reaction was employed to assess RNA expression of the target genes in 24 sporadic insulinomas: 15 grade 1 (G1), six grade 2 (G2) and three hepatic metastases. Somatic mutations of MET gene were searched by direct sequencing of exons 2, 10, 14, 16, 17 and 19. Results: Overexpression of MET was observed in the three hepatic metastases concomitantly with upregulation of the genes encoding HGF and matriptase and downregulation of SPINT1. A positive correlation was observed between MET RNA expression and Ki-67 proliferation index while a negative correlation was detected between SPINT1 expression and the mitotic index. No somatic mutations were found in MET gene. Conclusion: The final effect of the increased expression of HGF, its activator (matriptase) and its specific receptor (MET) together with a decreased expression of one potent inhibitor of matriptase (SPINT1) is probably a contribution to tumoral progression and metastatization in insulinomas.
Palavras-chave
Insulinoma, Hepatocyte growth factor, MET receptor, Gene expression, Somatic mutation
URI
https://observatorio.fm.usp.br/handle/OPI/12299
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCG
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/14
Artigos e Materiais de Revistas Científicas - LIM/25
Artigos e Materiais de Revistas Científicas - LIM/36
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