Brain-Specific Angiogenesis Inhibitor 1 is a Putative Factor for Inhibition of Neovascular Formation in Renal Cell Carcinoma

Abstract

Renal cell carcinoma is a typical hypervascular tumor in which neovascularization may have a large part in progression. We examined expression of the cancer regulating, p53 targeted angiogenesis inhibitor brain-specific angiogenesis inhibitor 1 in renal cell carcinoma tissue to elucidate the clinical significance of its expression. We examined brain-specific angiogenesis inhibitor 1 mRNA and protein expression in 47 renal cell carcinoma and 10 normal kidney tissues using real-time quantitative polymerase chain reaction and immunohistochemistry, respectively. Levels of VEGF and bFGF mRNA, and immunohistochemical expression of p53 protein were also investigated in the same renal cell carcinoma tissues. A significant decrease in BAI1 mRNA was noted in renal cell carcinoma tissue compared with that in normal kidney tissue (p <0.001). Immunostaining for brain-specific angiogenesis inhibitor 1 was also decreased in carcinoma tissue compared with normal kidney tissue. BAI1 mRNA and protein expression were lower in advanced renal cell carcinoma (pT3-4) than in localized renal cell carcinoma (pT1-2) tissues (p <0.03 and 0.003, respectively). A significant negative correlation was observed between microvessel density and brain-specific angiogenesis inhibitor 1 protein expression (r = -0.4056, p = 0.002). No significant correlation was noted between BAI1 and VEGF or bFGF mRNA levels. Brain-specific angiogenesis inhibitor 1 protein expression did not correlate with p53 protein expression. These observations suggest that down-regulation of brain-specific angiogenesis inhibitor 1 expression may be a critical factor in renal cell carcinoma development and BAI1 may be a promising candidate for gene therapy of renal cell carcinoma.