Publication: Increased expression of 5-lipoxygenase is common in clear cell renal cell carcinoma
Loading...
Date
2007
Authors
Faronato, M. ; Muzzonigro, G. ; Milanese, G. ; Menna, C. ; Bonfigli, A.R. ; Catalano, A. ; Procopio, A.
item.page.secondaryauthor
item.page.director
Publisher
Murcia : F. Hernández
publication.page.editor
publication.page.department
DOI
item.page.type
info:eu-repo/semantics/article
Description
Abstract
The clinical behaviour of Clear Cell Renal
Cell Carcinoma (CC-RCC) is often unpredictable. To
fully understand the signaling pathways involved in CCRCC
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 upregulation
is an important step in renal cancer progression.
publication.page.subject
Citation
item.page.embargo
Ir a Estadísticas
Sin licencia Creative Commons.