Open AccessUpregulation of nuclear PA28γ expression in cirrhosis and hepatocellular carcinoma
Author(s) -
Motoi Kondo,
Kohji Moriishi,
Hiroshi Wada,
Takehiro Noda,
Shigeru Marubashi,
Kenichi Wakasa,
Yoshiharu Matsuura,
Yuichiro Doki,
Masaki Mori,
Hiroaki Nagano
Publication year - 2011
Publication title -
experimental and therapeutic medicine
Language(s) - English
Resource type - Journals
eISSN - 1792-1015
pISSN - 1792-0981
DOI - 10.3892/etm.2011.415
Subject(s) - hepatocellular carcinoma , cirrhosis , cancer research , hccs , oncogene , molecular medicine , biology , pathology , cancer , medicine , cell cycle
We previously reported that proteasome activator 28γ (PA28γ) is an oncogenic protein in hepatitis C virus (HCV) core protein transgenic mice. The aim of this study was to determine the role of PA28γ expression at the protein level in the development and progression of human hepatocarcinogenesis and hepatocellular carcinoma (HCC). Samples from tissues representing a wide spectrum of liver disease were analyzed, including histologically normal livers (n=5), HCV-related chronic hepatitis (CH) (n=15) and cirrhosis (n=31). The level of nuclear PA28γ increased with the progression of liver disease from CH to cirrhosis. The majority of cirrhotic livers (68%; 21/31) displayed high nuclear PA28γ expression. However, in half of the HCCs (50%; 18/36), little or no nuclear PA28γ expression was observed, while the remaining 50% (18/36) of the cases displayed high levels of nuclear PA28γ expression. A clinicopathological survey demonstrated a significant correlation between nuclear PA28γ expression and capsular invasion in HCC (P=0.026); a striking difference was found between nuclear PA28γ expression in non-tumor tissues and shorter disease-free survival (P<0.01). Moreover, nuclear PA28γ expression in non-tumor tissues correlated with the expression of molecules related to the genesis of hepatic steatosis and HCC, such as sterol regulatory element binding protein-1c mRNA. The findings suggest the involvement of nuclear PA28γ expression in the progression and relapse of HCC, and suggest that nuclear PA28γ is a potentially suitable target for the prevention and/or treatment of HCC.