Expression of p33(ING1) in hepatocellular carcinoma: relationships to tumour differentiation and cyclin E kinase activity.
BACKGROUND
Inhibitor of growth-1 (ING1) is a new candidate for the tumour suppressor gene that encodes a 33k Da protein (p33(ING1)). While reduction of p33(ING1) is an important event in some human cancers, the expression of p33(ING1) in human hepatocellular carcinoma (HCC) remains to be examined. We evaluated p33(ING1) expression in various liver diseases including HCC.


METHODS
Expression of p33(ING1) was evaluated immunohistochemically not only in the normal liver (n = 5), but also in specimens of chronic hepatitis (n = 39) and HCC (n = 86). We also analysed the relationship between p33(ING1) expression and cyclin E kinase activity detected by autoradiography in 29 HCCs.


RESULTS
Expression of p33(ING1) was reduced in HCC, especially in moderately and poorly differentiated HCCs, and those at advanced stages. Furthermore, expression of p33(ING1) correlated inversely with cyclin E kinase activity.


CONCLUSIONS
These data suggest that reduction of p33(ING1) may contribute to the process of malignant transformation, progression and dedifferentiation of HCC via an increase of cyclin E kinase activity.
Ohgi
T
T
Third Dept. of Internal Medicine, Kagawa Medical University, Miki-cho, Kita-gun, Kagawa, Japan.
Masaki
T
T
Nakai
S
S
Morishita
A
A
Yukimasa
S
S
Nagai
M
M
Miyauchi
Y
Y
Funaki
T
T
Kurokohchi
K
K
Watanabe
S
S
Kuriyama
S
S
D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins; D019927:Cyclin E / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005260:Female; D016147:Genes, Tumor Suppressor; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D011506:Proteins / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D019927:Cyclin E; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; D018844:Cyclin-Dependent Kinases