Expression of HNF-1 alpha and HNF-1 beta in various histological differentiations of hepatocellular carcinoma.
Hepatic nuclear factor 1 (HNF-1) regulates genes in a hepatocyte-specific manner. It has been previously reported that the ratio of HNF-1 alpha and HNF-1 beta mRNA is related to histological differentiation hepatocellular carcinoma (HCC). In this study, the expression levels of the HNF-1 alpha and HNF-1 beta proteins were analysed relatively and quantitatively in various histologically differentiated HCC and surrounding non-cancerous tissues, and HNF-1 alpha binding activity for the AT element of the B domain of the human alpha-fetoprotein enhancer was examined. Western blot analysis demonstrated that HNF-1 alpha protein was expressed at a higher level in well-differentiated HCC tissues than in the surrounding non-HCC tissues; on the other hand, the HNF-1 alpha protein was expressed at lower levels in moderately and poorly differentiated HCCs than in the surrounding non-HCC tissues. The levels of HNF-1 beta expression in well-differentiated and poorly differentiated HCCs were similar to and higher than those found in the respective surrounding non-cancerous portions. In binding assays, HNF-1 binding activity was high in well-differentiated HCC and lower in moderately and poorly differentiated HCCs. Most well-differentiated HCC cases showed immunohistochemical expression of HNF-1 alpha. These findings show that poor histological differentiation of HCC correlates with decreases in the level and activity of HNF-1 alpha proteins.
Wang
W
W
First Division of Pathology, Kobe University School of Medicine, Japan.
Hayashi
Y
Y
Ninomiya
T
T
Ohta
K
K
Nakabayashi
H
H
Tamaoki
T
T
Itoh
H
H
D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta