title: Expression and correlation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor and microvessel density in experimental rat hepatocarcinogenesis.
abstract: An experimental rat hepatocellular carcinoma (HCC) model was established using diethylnitrosamine and N-nitrosomorpholine to induce carcinogenesis in Sprague-Dawley rats. During hepatocarcinogenesis, seven rats were sacrificed at 0, 4, 8, 12 and 16 weeks and 10 rats were sacrificed at 20 weeks. The levels of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) protein and mRNA were examined by immunohistochemistry, Western blot and semi-quantitative reverse transcriptase-polymerase chain reaction at different stages in the rat HCC model. Twenty weeks after induction of hepatocarcinogenesis, the expression of HIF-1alpha and VEGF protein and mRNA significantly increased compared with week 0. Microvessel density (MVD) increased considerably once liver cancer developed. There was a significant positive correlation between MVD and both HIF-1alpha and VEGF, and between HIF-1alpha and VEGF levels. These results suggest that HIF-1alpha and VEGF play important roles in tumour occurrence and development during rat hepatocarcinogenesis, possibly through promoting tumour angiogenesis.
authors.affiliation: Centre for the Study of Liver Cancer, Affiliated Provincial Hospital, Anhui Medical University, Hefei, China.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: G-L
authors.initials: GL
authors.lastname: Xu
authors.forename: W-D
authors.initials: WD
authors.lastname: Jia
authors.forename: Z-H
authors.initials: ZH
authors.lastname: Wang
authors.forename: J-S
authors.initials: JS
authors.lastname: Li
authors.forename: J-L
authors.initials: JL
authors.lastname: Ma
authors.forename: Y-S
authors.initials: YS
authors.lastname: Ge
authors.forename: S-X
authors.initials: SX
authors.lastname: Xie
authors.forename: J-H
authors.initials: JH
authors.lastname: Yu
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism*; D055806:Microvessels / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A