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

Diabetology & Metabolic Syndrome

Ricardo Rodrigues Giorgi⁹  Daniel Giannella-Neto⁴  Maria Lucia Corrêa-Giannella⁷  Maria Adelaide Albergaria Pereira³  Sheila Aparecida Coelho Siqueira⁸  Estela Maria Novak⁵  Marcel Cerqueira Cesar Machado¹  Luciana Corrêa²  Maria Angela Henriques Zanella Fortes⁶  Paula Waki Lopes da Rosa⁶  Cahuê De Bernardis Murat⁶ 

[1] Laboratório de Emergências Clínicas (LIM-51) da FMUSP, São Paulo, Brazil;Departamento de Patologia Oral, Faculdade de Odontologia da Universidade de São Paulo, São Paulo, Brazil;Divisão de Endocrinologia do HC-FMUSP, São Paulo, Brazil;Programa de Pós-Graduação em Medicina, Universidade Nove de Julho—UNINOVE, São Paulo, Brazil;Laboratório de Biologia Molecular da Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, Brazil;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, São Paulo, 01246-903, SP, Brazil;Centro de Terapia Celular e Molecular (NUCEL/NETCEM) da FMUSP, São Paulo, Brazil;Divisão de Patologia do HC-FMUSP, São Paulo, Brazil;Programa de Pós Graduação em Ciências da Saúde, Universidade de Santo Amaro (UNISA), São Paulo, Brazil

关键词: Somatic mutation;    Gene expression;    MET receptor;    Hepatocyte growth factor;    Insulinoma;   

Others  :  1229631
DOI  :  10.1186/s13098-015-0079-3

 received in 2015-02-09, accepted in 2015-09-22,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Murat et al.

【 图 表 】

Fig.1.

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