Constitutive activation of nuclear factor ?B in hepatocellular carcinoma

Autor: Shao-Nan Huang, Yun-Fan Liaw, Tse-Ching Chen, B S Ya-Hui Chang, Dar-In Tai, Sun-Lung Tsai, Kenneth S.S. Chang
Rok vydání: 2000
Předmět:
Zdroj: Cancer. 89:2274-2281
ISSN: 1097-0142
0008-543X
DOI: 10.1002/1097-0142(20001201)89:11<2274::aid-cncr16>3.0.co;2-2
Popis: 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.
Databáze: OpenAIRE
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