Suppression of albumin and alpha-fetoprotein gene expression by butyrolactone I, a selective inhibitor of the cdk family, in HuH-7 human hepatoma cells.

Abstract	Butyrolactone I is a selective inhibitor of the cyclin-dependent kinase (cdk) family, cdk2 and cdc2 kinase. In the present study, the effect of butyrolactone I on expression of the albumin and alpha-fetoprotein (AFP) genes was investigated in HuH-7 human hepatoma cells. Butyrolactone I inhibited cell growth and arrested cells predominantly in G2/M phase. By Northern blot analysis, the levels of both albumin and AFP mRNA were suppressed dose-dependently by butyrolactone I. In transient chloramphenicol acetyltransferase plasmid transfection experiments, the albumin promoter activity and the AFP promoter and enhancer activities were suppressed by butyrolactone I. Consistent with this, the transcripts of hepatocyte nuclear factor-1 (HNF-1), a liver-specific transcription factor which transactivates these promoter and enhancer regions were reduced by butyrolactone I in a dose-dependent manner. These results indicate that butyrolactone I down-regulates both the albumin and the AFP gene transcription through the reduction of HNF-1 expression.
Authors	D Hida, K Nakata, Y Shima, K Migita, K Nakao, Y Kato, N Ishii, K Eguchi
Journal	Anticancer research (Anticancer Res) 1998 Nov-Dec Vol. 18 Issue 6A Pg. 4317-22 ISSN: 0250-7005 [Print] Greece
PMID	9891485 (Publication Type: Journal Article)
Chemical References	Enzyme Inhibitors RNA, Messenger Serum Albumin alpha-Fetoproteins butyrolactone I Chloramphenicol O-Acetyltransferase Cyclin-Dependent Kinases 4-Butyrolactone
Topics	4-Butyrolactone (analogs & derivatives, toxicity) Carcinoma, Hepatocellular Cell Cycle (drug effects) Cell Division (drug effects) Chloramphenicol O-Acetyltransferase (genetics) Cyclin-Dependent Kinases (antagonists & inhibitors) Enzyme Inhibitors (toxicity) G2 Phase Gene Expression Regulation, Neoplastic (drug effects) Genes, Reporter Humans Liver Neoplasms Mitosis RNA, Messenger (genetics) Serum Albumin (genetics) Transcription, Genetic Transfection Tumor Cells, Cultured alpha-Fetoproteins (genetics)

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