Chicken Anti-Human GFRa-3 polyclonal antibody

In contrast to the hereditary form of medullary thyroid carcinoma (MTC), little is known about the etiology of sporadic MTC, Somatic gain-of-function mutations in the RET proto-oncogene, encoding a receptor tyrosine kinase, are found in an average of 40% of sporadic MTC, We analysed 31 sporadic MTC for somatic and germline variants in GFRA1, GFRA2 and GFRA3 which encode the co-receptors of RET, Although there were no somatic mutations in any of the three genes, a sequence variant (-193C>G) in the 5'-UTR of GFRA1 was found in 15% of cases. Three patients were heterozygous (het); another three patients homozygous (hom) for the G variant. The G allele was not observed in 31 race-matched normal controls. Hence, the relative frequency of this variant in sporadic MTC cases and controls differed significantly (P<0.05). Since this variant lies in the 5' UTR, likely at the transcriptional start site, we analysed for differential expression of GFR-1 at the transcript and protein levels. At the mRNA level, GFRA1 was over-expressed in tumors harboring the rare variant (P=0.06), The presence of the G polymorphic allele seemed to be associated with increased expression by immunostaining for GFR alpha -1. Interestingly, cytoplasmic staining was stronger in intensity for het patients and nuclear staining predominant in hom cases. In conclusion, mutation analysis of GFRA1, GFRA2 and GFRA3 revealed over-representation of a rare variant in GFRA1 (- 193C > G) in the germline of sporadic MTC cases. Our data suggest that the mechanism is related to over-expression of GFR alpha -1 and differential subcellular compartmentalization but the precise mechanism as to how it acts as a low penetrance susceptibility allele for the development of sporadic MTC remains to be elucidated.

Artemin, a member of the glial cell line-derived neurotrophic factor family, is an important cytokine and a critical participant in trigeminal pain disorders such as tongue pain and migraine. However, the mechanisms underlying artemin's activity are largely unknown. In the present study, we used primary cultured trigeminal ganglion neurons (TGNs) to determine the effect of artemin on the expression of the inducible form of nitric oxide synthase (iNOS), which is released in response to painful and inflammatory stimuli. Following artemin treatment, western blot analysis showed that the protein level of iNOS was transiently elevated after artemin treatment for 15 min (p < 0.05). Immunofluorescence revealed that both the expressions of iNOS and GFRa3 were significantly up-regulated after artemin treatment for 15 min. In addition, iNOS expression induced by artemin was co-localized with GFRa3 and TUJ-1 in primary cultured TGNs, respectively. Our results indicate a previously unknown role of artemin in regulating iNOS expression in primary cultured TGNs, and regulation of iNOS might be involved in the mechanism through which artemin participates in the trigeminal pain pathway.