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Constitutive activation of nuclear factor κB in hepatocellular carcinoma
Author(s) -
Tai DarIn,
Tsai SunLung,
Chang YaHui,
Huang ShaoNan,
Chen TseChing,
Chang Kenneth S. S.,
Liaw YunFan
Publication year - 2000
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20001201)89:11<2274::aid-cncr16>3.0.co;2-2
Subject(s) - carcinogenesis , nuclear protein , hepatocellular carcinoma , nuclear localization sequence , western blot , cell nucleus , hepatitis b virus , biology , immunohistochemistry , cancer research , transcription factor , microbiology and biotechnology , cytoplasm , medicine , pathology , cancer , virus , virology , gene , biochemistry , genetics
BACKGROUND Nuclear factor κB (NF‐κB) is a transcription factor that plays important roles in cell proliferation and in immunity against viral infections. NF‐κB is a dimer of Rel proteins that is sequestered in the cytoplasm as an inactive form through interaction with an inhibitory κB (IκB) protein. When IκB is degraded, the NF‐κB dimer will enter the nucleus to activate the target genes. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection may activate NF‐κB and, thus, may modulate cell apoptosis and may be associated with oncogenesis. The role of NF‐κB in hepatocellular carcinoma (HCC) has not yet been explored. METHODS Immunohistochemical staining to search for active nuclear RelA and nuclear IκBα proteins were done on formalin fixed liver tissues from 65 patients with HCC and from 9 normal control participants. Nuclear extracts of fresh‐frozen tumor and nontumor liver tissues from 37 patients with HCC and from 7 normal controls were tested for NF‐κB‐DNA binding activity by electrophoretic mobility shift assay. The RelA and IκBα protein expressions were studied by Western blot analysis. RESULTS Nuclear NF‐κB stainings were significantly more abundant in HBV‐infected or HCV‐infected tumors as well as nontumor parts of HCC compared with normal controls. Nuclear NF‐κB DNA binding activity and nuclear RelA protein expression were greater in tumor tissue compared with nontumor tissue, whereas cytosolic IκBα protein expression was generally greater in nontumor tissue compared with tumor tissue. CONCLUSIONS Constitutive activation of NF‐κB was found more frequently in tumor tissue compared with nontumor tissue. It is possible that NF‐κB overexpression accompanied by dysregulation of IκBα may play a role in the hepatocarcinogenesis of HBV or HCV infection. Cancer 2000;89:2274–81. © 2000 American Cancer Society.