Reduced expression and rare genomic alteration of nm23-H1 in human hepatocellular carcinoma and hepatoma cell lines.
We investigated the expression and genomic alteration of nm23-H1 (which encodes a nucleoside diphosphate, kinase A) in 12 human hepatocellular carcinomas (HCCs) and four hepatoma cell lines. The expression of nm23-H1 protein was significantly reduced in HCCs with intrahepatic metastasis (72%) compared with expression in HCCs without intrahepatic metastasis (38%). However, in two of three HCCs examined that had marked reduction of nm23-H1 protein, the nm23-H1 mRNA level was not reduced. A hepatoma cell line, HLF (phenotype, poorly differentiated carcinoma) revealed marked reduction of nm23-H1 protein compared with two other hepatoma cell lines, HuH-1 and HuH-2, although the mRNA level was similar in the three cell lines. No allelic deletion of the nm23-H1 gene was detected in the 12 HCCs examined. No point mutation in the coding region of the nm23-H1 gene was observed in any of the 12 HCCs or the four hepatoma cell lines. These findings suggest that: (i) the expression of nm23-H1 protein is inversely associated with high metastatic potential of HCC, (ii) regulation of nm23-H1 expression may occasionally occur at both the transcriptional and post-transcriptional levels in HCC; and (iii) genomic alteration of nm23-H1 is a rare event in HCC.
Fujimoto
Y
Y
Third Department of Internal Medicine, Asahikawa Medical College, Japan.
Ohtake
T
T
Nishimori
H
H
Ikuta
K
K
Ohhira
M
M
Ono
M
M
Kohgo
Y
Y
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015152:Blotting, Northern; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D017931:DNA Primers; D015536:Down-Regulation; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins; D009154:Mutation; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D017931:DNA Primers; D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins