Effect of c-fos antisense probe on prostaglandin E2-induced upregulation of vascular endothelial growth factor mRNA in human liver cancer cells.
OBJECTIVE
To examine the effect of prostaglandin E2 (PGE2) on the expression of vascular endothelial growth factor (VEGF) mRNA in the human hepatocellular carcinoma (HCC) HepG2 cells and the possible involvement of c-fos protein in this process.


METHODS
Human HCC HepG2 cells were divided into three groups treated respectively with PGE2, a combination of PGE2 and c-fos antisense oligodeoxynucleotide (ASO), and PGE2 plus c-fos sense oligodeoxynucleotide (SO). The expression of VEGF mRNA in HepG2 cells after different treatments was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The relative expression level of VEGF mRNA in HepG2 cells in each group was measured.


RESULTS
Administration of PGE2 resulted in an increased expression of c-fos and VEGF mRNA in HepG2 cells. The relative expression level of c-fos mRNA reached the peak at 3 h (68.4+/-4.7%) after PGE2 treatment, which was significantly higher than that at 0 h (20.6+/-1.7%, P<0.01). Whereas, the highest expression level of VEGF mRNA was observed at 6 h (100.5+/-6.1%) after PGE2 treatment, which was significantly higher than that at 0 h (33.2+/-2.4%, P<0.01). C-fos ASO significantly reduced PGE2-induced VEGF mRNA expression in HepG2 cells.


CONCLUSIONS
PGE2 increases the expression and secretion of VEGF in HCC cells by activating the transcription factor c-fos, promotes the angiogenesis of HCC and plays an important role in the pathogenesis of liver cancer.
Li
Yong-Qi
YQ
Comprehensive Diagnostic and Therapeutic Center, Xijing Hospital, the Fourth Military Medical University, Xi'an 710033, Shaanxi Province, China. yongqil33@yahoo.com.cn
Tao
Kai-Shan
KS
Ren
Ning
N
Wang
Yi-Hu
YH
D016375:Antisense Elements (Genetics); D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000503:physiopathology*; D045744:Cell Line, Tumor; D015232:Dinoprostone / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D016762:Genes, fos / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D016375:Antisense Elements (Genetics); D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D015232:Dinoprostone