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• W2070027802 abstract "No AccessJournal of UrologyInvestigative Urology1 Jun 2011Brain-Specific Angiogenesis Inhibitor 1 is a Putative Factor for Inhibition of Neovascular Formation in Renal Cell Carcinoma Toshikazu Izutsu, Ryuichiro Konda, Jun Sugimura, Kazuhiro Iwasaki, and Tomoaki Fujioka Toshikazu IzutsuToshikazu Izutsu More articles by this author , Ryuichiro KondaRyuichiro Konda More articles by this author , Jun SugimuraJun Sugimura More articles by this author , Kazuhiro IwasakiKazuhiro Iwasaki More articles by this author , and Tomoaki FujiokaTomoaki Fujioka More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.019AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: 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. Materials and Methods: 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. Results: 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. Conclusions: 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. References 1 : Levels of angiogenesis and expression of angiogenesis-related genes are prognostic for organ-specific metastasis of renal cell carcinoma. Cancer2005; 103: 931. Google Scholar 2 : Expression levels of genes that regulate metastasis and angiogenesis correlates with advanced pathological stage of renal cell carcinoma. Am J Pathol2001; 158: 735. Google Scholar 3 : Relation of microvessel density with microvascular invasion, metastasis and prognosis in renal cell carcinoma. BJU Int2007; 101: 758. Google Scholar 4 : The treatment of renal cell carcinoma with human leukocyte alpha-interferon. J Urol1983; 130: 1063. Link, Google Scholar 5 : Kidney cancer: identification of novel targets for therapy. Kidney Int2006; 69: 224. Google Scholar 6 : Targeting von Hippel-Lindau pathway in renal cell carcinoma. Clin Cancer Res2006; 12: 7215. Google Scholar 7 : Sorafenib in advanced clear-cell renal-cell carcinoma. N Eng J Med2007; 356: 125. Google Scholar 8 : Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Eng J Med2007; 356: 115. Google Scholar 9 : Targeted therapy for metastatic renal cell carcinoma. J Clin Oncol2006; 24: 5601. Google Scholar 10 : A novel brain-specific p53-target gene, BAI1, containing thrombospondin type 1 repeats inhibits experimental angiogenesis. Oncogene1997; 15: 2145. Google Scholar 11 : Extracellular fragment of brain-specific angiogenesis inhibitor 1 suppresses endothelial cell proliferation by blocking αvβ5 integrin. Exp Cell Res2004; 294: 172. Google Scholar 12 : Vasculostatin, a proteolytic fragment of brain angiogenesis inhibitor 1, is an antiangiogenic and antitumorigenic factor. Oncogene2005; 24: 3632. Google Scholar 13 : Brain-specific angiogenesis inhibitor1 expression is inversely correlated with vascularity and distant metastasis of colorectal cancer. Int J Oncol1998; 13: 967. Google Scholar 14 : Comparative study of angiostatic and anti-invasive gene expression as prognostic factors in gastric cancer. Int J Oncol2001; 18: 355. Google Scholar 15 : Vascularization is decreased in pulmonary adenocarcinoma expressing brain-specific angiogenesis inhibitor 1 (BAI1). Int J Molecul Med2000; 5: 181. Google Scholar 16 : Overexpression of the p53-inducible brain-specific angiogenesis inhibitor 1 suppresses efficiently tumour angiogenesis. Br J Cancer2002; 86: 490. Google Scholar 17 : Inhibition of tumor growth through suppression of angiogenesis by brain-specific angiogenesis inhibitor 1 gene transfer in murine renal cell carcinoma. Oncol Rep2007; 18: 785. Google Scholar 18 : Hepatocyte growth factor enhances vascular endothelial growth factor-induced angiogenesis in vitro and in vivo. Am J Pathol2001; 158: 1111. Google Scholar 19 : Brain angiogenesis inhibitor 1 is differentially expressed in normal brain and glioblastoma independently of p53 expression. Am J Pathol2003; 162: 19. Google Scholar Departments of Urology, Iwate Medical University School of Medicine, Morioka and Yamamoto Kumiai General Hospital (RK), Noshiro, Japan© 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 6June 2011Page: 2353-2358 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.Keywordsrenal cellmicrovesselskidneyBAI1 proteincarcinomagene therapyhumanMetricsAuthor Information Toshikazu Izutsu More articles by this author Ryuichiro Konda More articles by this author Jun Sugimura More articles by this author Kazuhiro Iwasaki More articles by this author Tomoaki Fujioka More articles by this author Expand All Advertisement PDF downloadLoading ..." @default.
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• W2070027802 title "Brain-Specific Angiogenesis Inhibitor 1 is a Putative Factor for Inhibition of Neovascular Formation in Renal Cell Carcinoma" @default.
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