Significance of VHL gene for Angiogenesis in Renal Cell Carcinoma

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Regulating molecule of angiogenesis, such as vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) have been investigated in renal cell carcinoma, because both the growth and metastases of renal cell carcinoma depend on the angiogenesis. On the other hand, VHL gene, which may be associated with a sporadic renal cell carcinoma, can regulate the angiogenesis via the control of the VEGF expression at a posttranscription level or negative control of the VEGF expression at a posttranscription level or negative control of TGF-α or -β1 by decreasing the stability of their mRNA. Furthermore, VHL gene products also regulate plasminogen activator urokinase (uPA), uPA receptor, plasminogen activator inhibitor-1, resulting in the inhibition of angiogenesis. These evidences suggest that VHL gene can play a significant role in the regulation of angiogenesis in renal cell carcinoma.To clarify the role of VHL gene in angiogenesis of renal cell carcinoma, we are estimating the microvessel density (MVD) and the expression of VHL gene in surgical specimen of renal cell carcinoma. MVD was estimated by immunohistostaining against anti VIII factor antibody. After cDNA of VHL gene was provided from Dr. Joe Gray, University of California San Francisco, we have been determining the expressing of VHL gene by in situ hybridization according to the methods described by Moch et al (Cancer Res. 58 : 2304-2309, 1998), but in situ hybridization did not work well. So far, we have not obtained the results enough to publish.