Expression of nuclear factor-kappaB family proteins in hepatocellular carcinomas.
OBJECTIVE
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.


METHODS
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.
O'Neil
Bert H
BH
Department of Medicine, Division of Hematology and Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Bert_oneil@med.unc.edu
Bůzková
Petra
P
Farrah
Hillary
H
Kashatus
David
D
Sanoff
Hanna
H
Goldberg
Richard M
RM
Baldwin
Albert S
AS
Funkhouser
William K
WK
D000081242:B-Cell Lymphoma 3 Protein; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D052003:NF-kappa B p52 Subunit / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors
D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051550:I-kappa B Kinase