Inhibitory effect of prostaglandin delta 12-PGJ2 on cell proliferation and alpha-fetoprotein expression in HuH-7 human hepatoma cells.
9-deoxy-delta 9,delta 12-13,14-dihydro-prostaglandin D2 (delta 12-PGJ2) is a potent inhibitor of proliferation of tumor cells. In the present study, the effect of delta 12-PGJ2 on the alpha-fetoprotein(AFP) and the albumin gene expression was analyzed in HuH-7 human hepatoma cells. delta 12-PGJ2 inhibited the cell growth and reduced the medium AFP concentrations dose-dependently. To determine whether this decline of AFP depends only on the relative decrease in cell numbers by delta 12-PGJ2, or is in part, due to the decrease in the cellular AFP synthesis by delta 12-PGJ2, Northern blot analysis was performed in this study. By Northern blotting, it was shown that delta 12-PGJ2 caused a marked reduction in the levels of the AFP mRNA and the albumin mRNA. In contrast, the level of the beta-actin mRNA was not changed by delta 12-PGJ2. In the transient chloramphnicol acetyltransferase plasmid transfection experiments, delta 12-PGJ2 did not suppress the AFP enhancer activity, which possibly regulates both the AFP and the albumin gene expression in HuH-7 hepatoma cells, but resulted in the selective repression of the AFP and the albumin promoter activity. These results suggest that delta 12-PGJ2 suppresses not only cell growth but also expression of the AFP gene and the albumin gene at the transcriptional level in human hepatoma cells.
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
S
S
Mitsuoka
A
A
Otsuru
K
K
Nakao
T
T
Tsutsumi
S
S
Tsuruta
K
K
Hamasaki
M
M
Shima
K
K
Nakata
T
T
Tamaoki
S
S
Nagataki
D000418:Albumins / Q000235:genetics; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011401:Promoter Regions, Genetic; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D000418:Albumins; D012333:RNA, Messenger; D000509:alpha-Fetoproteins; C037112:9-deoxy-delta-9-prostaglandin D2; D015500:Chloramphenicol O-Acetyltransferase; D015230:Prostaglandin D2