Expression and correlation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor and microvessel density in experimental rat hepatocarcinogenesis.
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.
Wang
W
W
Centre for the Study of Liver Cancer, Affiliated Provincial Hospital, Anhui Medical University, Hefei, China.
Xu
G-L
GL
Jia
W-D
WD
Wang
Z-H
ZH
Li
J-S
JS
Ma
J-L
JL
Ge
Y-S
YS
Xie
S-X
SX
Yu
J-H
JH
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*
D018952:Antigens, CD34; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A