Differential expression of genes encoding proteins of the HGF/MET system in insulinomas. Issue 1 (December 2015) - Murat, Cahuê
Abstract 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 andST14 (encode HGF activator and matriptase, respectively, two serine proteases that catalyze conversion of pro-HGF to active HGF); andSPINT1 andSPINT2 (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 ofMET gene were searched by direct sequencing of exons 2, 10, 14, 16, 17 and 19. Results Overexpression ofMET was observed in the three hepatic metastases concomitantly with upregulation of the genes encoding HGF and matriptase and downregulation ofSPINT1 . A positive correlation was observed betweenMET RNA expression and Ki-67 proliferation index while a negative correlation was detected betweenSPINT1 expression and the mitotic index. No somatic mutations were found inMET 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.