Expression ratio of hepatocyte nuclear factor-1 to variant hepatocyte nuclear factor-1 in differentiation of hepatocellular carcinoma and hepatoblastoma.
OBJECTIVE
Liver-specific protein genes have multiple cis-/trans-acting elements, but those accountable for hepatocytic differentiation are unclear. An AT-rich core sequence (AT motif) is essential as a cis-acting element for the hepatic transcription. Homologous proteins hepatocyte nuclear factor-1 (HNF-1) and variant HNF-1 (vHNF-1) bind to this motif. The ratio of HNF-1 to vHNF-1 mRNA was examined in various liver tissues with respect to their differentiation.


METHODS
The competitive reverse transcriptional polymerase chain reaction was employed to amplify HNF-1 and vHNF-1 mRNA simultaneously and to examine their expression ratio in total RNA extracted from frozen liver tissues of 37 patients with hepatocellular carcinoma, five patients with hepatoblastoma, and 15 non-neoplastic liver tissues.


RESULTS
The ratio of HNF-1 to vHNF-1 mRNA was higher in well-differentiated cases than in poorly-differentiated and undifferentiated cases, except that one poorly-differentiated hepatoblastoma displayed a high ratio. Non-neoplastic liver tissues had low ratios similar to poorly-differentiated hepatocellular carcinoma, the reason for which remained unknown. However, chronic hepatitis and liver cirrhosis cases also demonstrated low ratios, and hence degenerative changes themselves displayed no obvious influence on such ratios. Thus, the gene expression of HNF-1 and vHNF-1 seemed to be differentially regulated in neoplastic and non-neoplastic hepatocytes.


CONCLUSIONS
These results suggested that the ratio of HNF-1 to vHNF-1 mRNA correlated with histological differentiation of HCC and hepatoblastoma.
First Department of Pathology, Kobe University School of Medicine, Japan.
T
T
Ninomiya
Y
Y
Hayashi
K
K
Saijoh
K
K
Ohta
S
S
Yoon
H
H
Nakabayashi
T
T
Tamaoki
M
M
Kasuga
H
H
Itoh
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018197:Hepatoblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D007223:Infant; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000032:analysis; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D012334:RNA, Neoplasm; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta