Upregulation of nuclear PA28γ expression in cirrhosis and hepatocellular carcinoma

Abstract

Abstract. 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.

The Expression and Clinical Significance of PA28 γ in Colorectal Cancer

“…20 The nuclear PA28 γ is involved in the progression and the relapse of hepatocellular carcinoma. 27 It suggested that PA28 γ was a novel serum biomarker for the diagnosis of CRC 28 ; however, the reports above needed further validation by more experimental and clinical studies.…”

Increased proteasome activator 28 gamma (PA28γ) levels are unspecific but correlate with disease activity in rheumatoid arthritis

“…Wang et al [ 26 ] indicated an overexpression of PA28γ in breast cancer and demonstrated a relation of expression with cancer status and metastasis. Kondo et al [ 29 ] mentioned an increase of nuclear PA28γ with the progression of liver disease from hepatitis C virus related chronic hepatitis to liver cirrhosis. These findings suggest PA28γ as target for prevention and/or treatment of hepatocellular carcinoma.…”

“…Due to these functions it seems to be very likely that PA28γ is involved in carcinogenesis. Many studies revealed that PA28γ is overexpressed in different tumor tissues and serum samples of patients with diverse cancers affecting colon [ 24 , 25 ], breast [ 26 ], larynx [ 27 ], lung [ 28 ], liver [ 29 ] and thyroids [ 30 ]. Thus, PA28γ interferes with cell cycle, proliferation and invasion in poorly differentiated thyroid carcinoma cells [ 31 ].…”

Role of the ubiquitin-proteasome system in the progression of oral squamous cell carcinoma

“…Протеомное [44,45], колоректальном раке [46], гепатоцеллюлярной карциноме [47] и плоскоклеточном раке полости рта [48].…”