Significance of VHL gene for Angiogenesis in Renal Cell Carcinoma

肾细胞癌的生长和转移都依赖于血管生成，因此，血管内皮生长因子（VEGF）或碱性成纤维细胞生长因子（bFGF）等血管生成调控分子在肾细胞癌中的作用已被研究。另一方面，VHL基因可能与散发性肾细胞癌相关，它通过在转录后水平调控VEGF表达或在转录后水平负调控VEGF表达或负调控TGF-α或TGF-β1 mRNA的稳定性来调控血管生成。此外，VHL基因产物还调节纤溶酶原激活物尿激酶（uPA）、uPA受体、纤溶酶原激活物抑制剂-1，从而抑制血管生成。为探讨VHL基因在肾细胞癌血管生成中的作用，我们检测了肾细胞癌手术标本中VHL基因的表达和微血管密度（MVD）。抗Ⅷ因子抗体荧光染色法检测MVD。在从加州大学弗朗西斯科分校的Joe Gray博士提供VHL基因的cDNA后，我们根据Moch等（Cancer Res.58：2304-2309，1998）描述的方法通过原位杂交测定VHL基因的表达，但是原位杂交效果不好。到目前为止，我们还没有获得足够的结果来发表。

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.