Resumen de Increased expression of 5-lipoxygenase is common in clear cell renal cell carcinoma
M. Faronato, Giovanni Muzzonigro, G. Milanese, C. Menna, A.R. Bonfigli, A. Catalano, A. Procopio
Summary. The clinical behaviour of Clear Cell Renal Cell Carcinoma (CC-RCC) is often unpredictable. To fully understand the signaling pathways involved in CC-RCC development, we examined whether the 5-Lipoxygenase (5-LO), which catalyzes the biosynthesis of proinflammatory leukotrienes, is involved in renal tumorigenesis. By analyzing 46 snap-frozen primary renal cell carcinomas and their corresponding normal renal cortex biopsies, 5-LO protein levels were found to be significantly increased in the majority of CC-RCCs (P<0.001). Quantitative 5-LO mRNA expression analysis revealed up to 3-fold increased expression in the tumor tissues. There was no association between 5-LO and gender, grade or vein invasion. In contrast, increased 5-LO protein and mRNA correlated with large tumor size (>4 cm) and age of patients (P<0.001). 5-LO was frequently overexpressed in von Hippel-Lindau protein (pVHL)¿reduced tumors and in Vascular Endothelial Growth Factor (VEGF)-positive tumors, which represent two frequent alterations in CC-RCC. Cell culture experiments demonstrated that VEGF expression was strongly inducible by 5-LO metabolites in RCC cell lines. The loss of pVHL expression led to high basal 5-LO and VEGF expression, which were markedly reduced by transfection with 5-LO small interfering RNA (siRNA). These results suggest that 5-LO up-regulation is an important step in renal cancer progression. Histol Histopathol 22, 1109-1118 (2007)
