Expression of nuclear factor-kappaB family proteins in hepatocellular carcinomas
Bert H O'Neil1, Petra Bůzková, Hillary Farrah
1Department of Medicine, Division of Hematology and Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Bert_oneil@med.unc.edu
Purpose:
Nuclear factor-kappaB (NF-kappaB) has been shown to be abnormally activated in some human hepatocellular carcinomas (HCCs), but most studies of NF-kappaB in patient samples have focused on the p65 subunit. Recent information has implicated IkappaB family members (e.g. Bcl-3) as possible mediators of NF-kappaB activation. Therefore, we examined the expression of all NF-kappaB family members and downstream targets in HCC.
Study Design:
Archived HCCs from 30 patients were evaluated by immunohistochemistry for NF-kappaB family proteins, Bcl-3 and targets of NF-kappaB/IkappaB function. Results were validated by Western blotting in frozen paired HCC and adjacent normal tissue in a subset of cases.
Results:
NF-kappaB p50 and p52 subunits were frequently localized to tumor cell nuclei (40 and 48%), whereas p65 positivity was infrequent. Bcl-3 was overexpressed in 90% of tumor cell nuclei compared with 26% of adjacent non-neoplastic liver (p < 0.001).
Conclusions:
Aberrant Bcl-3 nuclear expression occurs in the vast majority of HCCs compared with adjacent normal or cirrhotic liver tissue. Bcl-3 is known to interact with NF-kappaB p50 and p52 homodimers, and our study demonstrates very frequent nuclear colocalization of Bcl-3 and p50/p52, suggesting that the Bcl-3/p50 or Bcl-3/p52 interactions are important in HCC pathogenesis.
More Related Videos
09:27Analysis of Liver Microenvironment During Early Progression of Non-Alcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma in Zebrafish
Published on: April 1, 2021
06:38An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Related Concept Videos
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-kB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Cell Specific Gene Expression
Co-activators and Co-repressors
Liver Regeneration
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...
Regulation of Nuclear Protein Sorting
