Activating mechanism of transcriptor NF-kappaB regulated by hepatitis B virus X protein in hepatocellular carcinoma.
OBJECTIVE
To investigate the mechanism and significance of NF-kappaB activation regulated by hepatitis B virus X protein (HBx) in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).


METHODS
The expression levels of HBx, p65, IkappaB-alpha and ubiquitin were detected by immunohistochemistry in HCC tissue microarrays (TMA) respectively, and IkappaB-alpha was detected by Western blot in HCC and corresponding liver tissues.


RESULTS
The percentage of informative TMA samples was 98.8% in 186 cases with a total of 367 samples. Compared with corresponding liver tissues (60.0%), the HBx expression was obviously decreased in HBV-associated HCC (47.9%, u=2.24, P<0.05). On the contrary, the expressions of p65 (20.6% vs 45.3%, u=4.85, P<0.01) and ubiquitin (8.9% vs 59.0%, u=9.68, P<0.01) were notably elevated in HCC. In addition, IkappaB-alpha had a tendency to go up. Importantly, positive relativity was observed between HBx and p65 (chi2=10.26, P<0.01), p65 and IkappaB-alpha (chi (2)=16.86, P<0.01), IkappaB-alpha and ubiquitin (chi2=8.90, P<0.01) in HCC, respectively.


CONCLUSIONS
Both active and non-active forms of NF-kappaB are increased in HBV-associated HCC. Variant HBx is the major cause of the enhancement of NF-kappaB activity. The activation always proceeds in nucleus and the proteasome complexes play an important role in the activation.
Wang
Tao
T
Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.
Wang
Yi
Y
Wu
Meng-Chao
MC
Guan
Xin-Yuan
XY
Yin
Zheng-Feng
ZF
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
D016328:NF-kappa B; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein