The enzymatic basis for the conversion of nonfucosylated to fucosylated alpha-fetoprotein by acyclic retinoid treatment in human hepatoma cells: activation of alpha1-6 fucosyltransferase.
The purpose of the present study was to investigate the mechanism by which nonfucosylated alpha-fetoprotein (AFP) is converted to fucosylated AFP in human hepatoma cell lines exposed to acyclic retinoid (AR), an effective drug for the secondary prevention of hepatocellular carcinoma. AR treatment (100 microM) of HepG2 and Hep3B cells significantly increased the activity and mRNA levels of alpha1-6 fucosyltransferase (alpha1-6 FucT), the enzyme responsible for the fucosylation of AFP, leading to an increase in fucosylated glycoproteins as evidenced by lectin binding measurements. Lectin immunoelectrophoresis of AFP obtained from culture media indicated that the relative percentage of nonfucosylated AFP (L1 fraction) was decreased and alpha1-6 fucosylated AFP (L3 fraction) was increased in these hepatoma cell lines after treatment with AR. The total AFP levels were, however, markedly suppressed by AR treatment, and therefore the absolute L3 fraction on the basis of the total AFP present was extremely low. These results demonstrate that AR enhances the conversion of the L1 to the L3 fraction due to the activation of alpha1-6 FucT in human hepatoma cell lines despite clinical outcome with AR treatment and the L3 fraction of AFP. Even though the dramatic decrease in AFP is the limiting factor in the synthesis of the L3 fraction and, therefore, the absolute value of fucosylated AFP is extremely low, the conversion from L1 to L3 as judged by lectin immunoelectrophoresis represents a good marker for the progress of AR treatment.
Noda
K
K
Department of Biochemistry, Division of Molecular Therapy Science, Osaka University Graduate School of Medicine, Osaka, Japan.
Miyoshi
E
E
Kitada
T
T
Nakahara
S
S
Gao
C-X
CX
Honke
K
K
Shiratori
Y
Y
Moriwaki
H
H
Sasaki
Y
Y
Kasahara
A
A
Hori
M
M
Hayashi
N
N
Taniguchi
N
N
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D002240:Carbohydrate Sequence; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D004586:Electrophoresis; D005643:Fucose / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism; D008954:Models, Biological; D008956:Models, Chemical; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology; D013997:Time Factors; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000378:metabolism*
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D012176:Retinoids; D000509:alpha-Fetoproteins; D005643:Fucose; D014212:Tretinoin; C034534:3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid