Expression of hypoxia-inducible factor 3α in hepatocellular carcinoma and its association with other hypoxia-inducible factors.
The functional role of hypoxia-inducible factor (HIF)-3α in the development of hepatocellular carcinoma (HCC) is not yet fully understood. The aim of the present study was to elucidate the association between HIF-3α expression and the clinicopathological features as well as prognosis of HCC patients. In addition, we investigated the association between HIF-3α expression and the expression of HIF-1α and HIF-2α in tumor tissues. The protein levels of HIF-3α were determined using immunohistochemical analysis of paraffin sections of 126 paired HCC and peritumoral tissues. PLC/PRF/5 cells, a human HCC cell line, were transfected with HIF-1α and HIF-2α vectors and HIF-3α mRNA and protein expression was detected using quantitative polymerase chain reaction and western blot analysis, respectively. The expression of HIF-3α was upregulated in 46.0% (58/126) and downregulated in 42.9% (54/126) of tumor tissues, respectively, when compared to peritumoral tissues. HIF-3α protein expression was not associated with peripheral blood vessel invasion, overall survival, or disease-free survival in HCC patients (P>0.05). In HCC tissues, the levels of HIF-3α protein were positively correlated with HIF-2α, but not with HIF-1α expression in HCC tissues. HIF-3α was upregulated in PLC/PRF/5 and Hep3B cells overexpressed with HIF-1α or HIF-2α. The hypoxic microenvironment of liver cancer did not lead to elevated HIF-3α protein expression, indicating that HIF-3α is regulated differently from HIF-1αin vivo. The correlation between HIF-3α and HIF-2α expression at the cellular and tissue levels indicated that HIF-3α may be a target gene of HIF-2α. The hypoxic microenvironment did not lead to elevation of HIF-3α protein expression in liver cancer; thus, HIF-3α may be a target gene of HIF-2α.
Department of Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, P.R. China.
Ping
P
Liu
Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Xiefan
X
Fang
Department of Pharmacy, Mercy Medical Center-Clinton, Clinton, IA 52732, USA.
Yang
Y
Song
Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550001, P.R. China.
Jian-Xin
JX
Jiang
Department of General Surgery, The Center Hospital of Huanggang, Huanggang, Hubei 438000, P.R. China.
Qian-Jin
QJ
He
Department of Rehabilitation, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, P.R. China.
Xiang-Jie
XJ
Liu
hepatocellular carcinoma; hypoxia-inducible factor-1α; hypoxia-inducible factor-2α; hypoxia-inducible factor-3α; prognosis