Expression of liver-enriched nuclear factors and their isoforms in alpha-fetoprotein-producing gastric carcinoma cells.
Alpha-fetoprotein (AFP)-producing gastric cancer (AFP-GC) is a highly malignant variant of adenocarcinoma with aberrant hepatocellular phenotype. A detailed understanding of the regulation of its liver phenotype is lacking. Liver-enriched nuclear factors (LENFs) are implicated in the transcriptional regulation of AFP in the fetal liver. To investigate the regulatory role of LENFs in AFP-GCs, the expression of LENFs including CCAAT/enhancer binding protein (C/EBP)-beta, C/EBP-alpha, hepatocyte nuclear factor (HNF)-1alpha, HNF-1beta and HNF-4alpha was investigated in 3 cell lines of AFP-GC and 7 cell lines of control GC. The liver activating protein (LAP), an activating isoform of C/EBP-beta, was predominantly expressed in AFP-GCs, whereas the liver inhibitory protein (LIP), an inhibitory isoform of C/EBP-beta, predominated in the control GCs. HNF-1alpha was relatively suppressed in AFP-GCs. HNF-4alpha was expressed in one of three AFP-GC cell lines. C/EBP-alpha and HNF-1beta were expressed at the same levels in both cell types of GC. AFP-GCs expressed a set of hepatocyte-related proteins (e.g., transferrin and albumin) while they still retained the several glandular cell-related proteins (e.g., MUC2). The induction of LIP reduced transferrin expression and induced CEA expression in an AFP-GC line. Collecting these results, it was suggested that the contribution of LENFs, especially isoforms of C/EBP-beta, is possibly important in phenotypic regulation of AFP-GCs.
Supriatna
Yana
Y
Department of Molecular Pathology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Kishimoto
Takashi
T
Furuya
Mitsuko
M
Tochigi
Naobumi
N
Ishiguro
Hiroshi
H
Tosh
David
D
Ishikura
Hiroshi
H
D000230:Adenocarcinoma / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D051536:Hepatocyte Nuclear Factors / Q000096:biosynthesis*; D006801:Humans; D020033:Protein Isoforms / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism*; D014162:Transfection; D000509:alpha-Fetoproteins / Q000096:biosynthesis*
D051536:Hepatocyte Nuclear Factors; D020033:Protein Isoforms; D000509:alpha-Fetoproteins