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

Autor: Murat Cde B; Laboratório de Endocrinologia Celular e Molecular (LIM-25) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), Av. Dr. Arnaldo, 455, 01246-903 São Paulo, SP Brazil., da Rosa PW; Laboratório de Endocrinologia Celular e Molecular (LIM-25) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), Av. Dr. Arnaldo, 455, 01246-903 São Paulo, SP Brazil., Fortes MA; Laboratório de Endocrinologia Celular e Molecular (LIM-25) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), Av. Dr. Arnaldo, 455, 01246-903 São Paulo, SP Brazil., Corrêa L; Departamento de Patologia Oral, Faculdade de Odontologia da Universidade de São Paulo, São Paulo, Brazil., Machado MC; Laboratório de Emergências Clínicas (LIM-51) da FMUSP, São Paulo, Brazil., Novak EM; Laboratório de Biologia Molecular da Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, Brazil., Siqueira SA; Divisão de Patologia do HC-FMUSP, São Paulo, Brazil., Pereira MA; Divisão de Endocrinologia do HC-FMUSP, São Paulo, Brazil., Corrêa-Giannella ML; Laboratório de Endocrinologia Celular e Molecular (LIM-25) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), Av. Dr. Arnaldo, 455, 01246-903 São Paulo, SP Brazil ; Centro de Terapia Celular e Molecular (NUCEL/NETCEM) da FMUSP, São Paulo, Brazil., Giannella-Neto D; Programa de Pós-Graduação em Medicina, Universidade Nove de Julho-UNINOVE, São Paulo, Brazil., Giorgi RR; Laboratório de Endocrinologia Celular e Molecular (LIM-25) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), Av. Dr. Arnaldo, 455, 01246-903 São Paulo, SP Brazil ; Programa de Pós Graduação em Ciências da Saúde, Universidade de Santo Amaro (UNISA), São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Diabetology & metabolic syndrome [Diabetol Metab Syndr] 2015 Oct 01; Vol. 7, pp. 84. Date of Electronic Publication: 2015 Oct 01 (Print Publication: 2015).
DOI: 10.1186/s13098-015-0079-3
Abstrakt: 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.
Databáze: MEDLINE
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