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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Differential expression of erythropoietin and its receptor in von hippel-lindau-associated and multiple endocrine neoplasia type 2-associated pheochromocytomas.

Pheochromocytoma is a neuroendocrine tumor associated with a variety of genetic disorders, which include von Hippel-Lindau disease (VHL), multiple endocrine neoplasia type 2 (MEN 2), neurofibromatosis type 1, hereditary paraganglioma, and succinate dehydrogenase gene-related tumors. Previous studies of VHL-associated and MEN 2-associated pheochromocytomas suggest morphological, biochemical, and clinical differences exist among the tumors, but the process by which they develop remains unclear. Studies in other VHL- associated tumors suggest that VHL gene deficiency causes coexpression of erythropoietin (Epo) and its receptor (Epo-R), which facilitates tumor growth. The objective of this study was to understand the different process of tumorigenesis for VHL and MEN 2-associated pheochromocytomas. Ten pheochromocytomas (VHL patients n = 5, MEN 2 patients n = 5) were examined for the presence or absence of Epo and Epo-R using Western blot, immunohistochemistry, and RT-PCR analyses. Coexpression of Epo and Epo-R was found in all five VHL-associated pheochromocytomas; in contrast, expression of Epo-R, but not Epo, was documented in all five MEN 2-associated pheochromocytomas. Expression of Epo appears to be a result of VHL gene deficiency, possibly through activation of the hypoxia inducible factor-1 pathway, whereas Epo-R is an embryonal marker whose sustained expression in both VHL- and MEN 2-associated pheochromocytomas reflects an arrest or defect in development. These findings suggest an alternative process of tumorigenesis in VHL- and MEN 2- associated pheochromocytomas and implicate Epo as a clinical biomarker to differentiate these tumors.[1]

References

  1. Differential expression of erythropoietin and its receptor in von hippel-lindau-associated and multiple endocrine neoplasia type 2-associated pheochromocytomas. Vogel, T.W., Brouwers, F.M., Lubensky, I.A., Vortmeyer, A.O., Weil, R.J., Walther, M.M., Oldfield, E.H., Linehan, W.M., Pacak, K., Zhuang, Z. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
 
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