PMID- 10098638 OWN - NLM STAT- MEDLINE DCOM- 19990603 LR - 20170214 IS - 0300-9858 (Print) IS - 0300-9858 (Linking) VI - 36 IP - 2 DP - 1999 Mar TI - Expression of vascular endothelial growth factor in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced rat bladder carcinogenesis. PG - 111-6 AB - Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are proteins implicated in tumor-associated microvascular angiogenesis. Expressions of VEGF and bFGF in various stages of chemical-induced rat bladder carcinogenesis were immunohistochemically investigated. Thirty-two male 6-week-old Wistar rats were given drinking water containing 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 20 weeks. VEGF and bFGF were not detected in the normal bladder epithelium. In simple hyperplasia, intensive expression of VEGF was observed in a few epithelial cells, and the expression of epithelial VEGF became more pronounced in papillary or nodular (PN) hyperplasia and papilloma. In carcinoma, heterogeneous expression of VEGF was observed in focal tumor cells, intensely expressed in the invading tumor cells. Ultrastructurally, carcinoma cells showed VEGF immunoreactivity in the cytoplasmic matrix and some rough endoplasmic reticulum, and VEGF-positive and -negative carcinoma cells were also clearly defined. High levels of VEGF mRNA were observed in the carcinoma. However, bFGF was not detected in the epithelium throughout the carcinogenesis. Increased microvessel counts appeared at simple hyperplasia and became more pronounced in PN hyperplasia, papilloma, and carcinoma (F-test; P < 0.05). In the carcinoma, the microvessel counts of the VEGF-expressing tumor areas were significantly higher than that of the non-VEGF-expressing tumor areas (U-test; P < 0.05). The present study suggests that upregulation of epithelial VEGF may begin at a quite early stage in BBN-induced rat bladder carcinogenesis, but bFGF may not be involved. FAU - Wakui, S AU - Wakui S AD - Comparative Toxicology Laboratories, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan. wakui@azabu-u.ac.jp FAU - Furusato, M AU - Furusato M FAU - Sasaki, S AU - Sasaki S FAU - Muto, T AU - Muto T FAU - Takahashi, H AU - Takahashi H FAU - Masaoka, T AU - Masaoka T FAU - Ushigome, S AU - Ushigome S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Vet Pathol JT - Veterinary pathology JID - 0312020 RN - 0 (Antibodies, Monoclonal) RN - 0 (Carcinogens) RN - 0 (Endothelial Growth Factors) RN - 0 (Lymphokines) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (Vascular Endothelial Growth Factors) RN - 0 (von Willebrand Factor) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 3817-11-6 (Butylhydroxybutylnitrosamine) SB - IM MH - Animals MH - Antibodies, Monoclonal MH - Blotting, Northern/veterinary MH - Butylhydroxybutylnitrosamine MH - Carcinogens MH - Endothelial Growth Factors/genetics/*metabolism MH - Fibroblast Growth Factor 2/genetics/metabolism MH - *Gene Expression Regulation MH - Immunohistochemistry MH - Lymphokines/genetics/*metabolism MH - Male MH - Microscopy, Electron/veterinary MH - Neovascularization, Pathologic/veterinary MH - Rats MH - Rats, Wistar MH - Urinary Bladder/immunology/pathology MH - Urinary Bladder Neoplasms/blood supply/chemically induced/metabolism/*veterinary MH - Vascular Endothelial Growth Factor A MH - Vascular Endothelial Growth Factors MH - von Willebrand Factor/immunology EDAT- 1999/03/31 00:00 MHDA- 1999/03/31 00:01 CRDT- 1999/03/31 00:00 PHST- 1999/03/31 00:00 [pubmed] PHST- 1999/03/31 00:01 [medline] PHST- 1999/03/31 00:00 [entrez] AID - 10.1354/vp.36-2-111 [doi] PST - ppublish SO - Vet Pathol. 1999 Mar;36(2):111-6. doi: 10.1354/vp.36-2-111.