Tumors of the central nervous system (CNS) often have sustained expression of 
labile genes, including angiogenic growth factors and immunosuppressive 
cytokines, which promote tumor progression. Stabilization of the RNA transcripts 
for these genes, such as vascular endothelial growth factor (VEGF), is an 
important molecular pathway for this up-regulation. HuR, a member of the Elav 
family of RNA-binding proteins, has been implicated in this pathway through its 
binding to adenine and uridine (AU)-rich stability elements (ARE) located in the 
3' untranslated regions (3'-UTRs) of the mRNA. Whereas three of the Elav family 
members (Hel-N1, HuC, and HuD) are restricted to young and mature neurons, HuR 
is more broadly expressed, including proliferating cells of the developing CNS. 
Because RNA stabilization of labile genes may promote tumor growth, we analyzed 
and compared the expression pattern of HuR in 35 freshly resected and cultured 
CNS tumors to determine whether there was any correlation with tumor grade or 
histological type. We found that HuR mRNA was consistently expressed in all of 
the tumors, regardless of cell origin or degree of malignancy. Using a novel 
HuR-specific polyclonal antibody, we found that strong HuR protein expression 
was limited to high-grade malignancies (glioblastoma multiforme and 
medulloblastoma). Within the glioblastoma multiforme, prominent HuR expression 
was also detected in perinecrotic areas in which angiogenic growth factors are 
up-regulated. To further define its role as a potential RNA stabilizer, we 
analyzed whether HuR could bind to the stability motifs within the 3'-UTRs of 
cytokines and growth factors linked to brain tumor progression. We used a novel 
ELISA-based RNA binding assay and focused on the 3'-UTRs of angiogenic factors 
VEGF, COX-2, and (interleukin) IL-8 as well as the immunomodulating factors 
IL-6, transforming growth factor (TGF)-beta and tumor necrosis factor 
(TNF)-alpha as potential RNA ligands. Our results indicated overall a very high 
binding affinity to these RNA targets. A comparison of these ligands revealed a 
hierarchy of binding affinities with the angiogenic factors, and TGF-beta 
showing the highest (Kd of 1.8-3.4 nM), and TNF-alpha the lowest (Kd of 18.3 
nM). The expression pattern of HuR, coupled with the RNA binding data, strongly 
suggests a role for this protein in the posttranscriptional regulation of these 
genes in CNS tumors.