Regulation of albumin and alpha-fetoprotein gene expression by colloid osmotic pressure in human hepatoma cells.
BACKGROUND
Colloid osmotic pressure has been thought to regulate albumin synthesis; however, the exact mechanism remains obscure. In the present study, the effect of colloid osmotic pressure on the albumin and alpha-fetoprotein gene expression in HuH-7 human hepatoma cells was analyzed.


METHODS
HuH-7 cells were treated with albumin or dextran (mean mol wt, 70,000), and changes in the levels of albumin and alpha-fetoprotein messenger RNA (mRNA) were analyzed by Northern blotting. Furthermore, in transient chloramphenicol acetyltransferase (CAT) plasmid transfection experiments, effects of colloid osmotic pressure on CAT activities were studied.


RESULTS
By Northern blot analysis, the levels of both albumin and alpha-fetoprotein mRNA were dose-dependently suppressed by the elevation of colloid osmotic pressure and returned to pretreatment levels 48 hours after the culture medium containing dextran was replaced with a dextran-free fresh medium. In transient CAT plasmid transfection experiments, the increased level of colloid osmotic pressure resulted in the repression of both albumin and alpha-fetoprotein promoter activities. In contrast, alpha-fetoprotein enhancer activity, which possibly regulates not only alpha-fetoprotein but also albumin gene expression, was not affected by changes in colloid osmotic pressure.


CONCLUSIONS
These results suggest that colloid osmotic pressure regulates both albumin and alpha-fetoprotein gene transcription through the modulation of their promoter activities.
Tsutsumi
T
T
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Nakao
K
K
Mitsuoka
S
S
Hamasaki
K
K
Tsuruta
S
S
Shima
M
M
Nakata
K
K
Tamaoki
T
T
Nagataki
S
S
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002455:Cell Division; D003102:Colloids / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009997:Osmotic Pressure; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012709:Serum Albumin / Q000235:genetics*; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000235:genetics*
D003102:Colloids; D012333:RNA, Messenger; D012709:Serum Albumin; D000509:alpha-Fetoproteins