Vitamin K-dependent carboxylase activity, prothrombin mRNA, and prothrombin production in two cultured rat hepatoma cell lines.
The presence of under-gamma-carboxylated forms of plasma prothrombin is a marker for human primary hepatocellular carcinoma. A rat hepatoma cell line (7777) which was previously shown to secrete undercarboxylated prothrombin when grown as a solid tumor has now been grown in monolayer culture. This cell line has a decreased activity of the microsomal vitamin K-dependent carboxylase when compared to a control (H4IIEC3) hepatoma line, does not increase intracellular prothrombin concentrations in response to vitamin K depletion, and secretes undercarboxylated prothrombin even when grown in vitamin K supplemented media. Prothrombin gene expression in the 7777 cell line, as measured by prothrombin mRNA levels, was not altered in the 7777 cell line. This cell line appears to be a model for assessing the cellular alterations responsible for undercarboxylated prothrombin excretion by human hepatocellular tumors.
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison 53706.
D V
DV
Shah
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Zhang
J A
JA
Engelke
A U
AU
Bach
J W
JW
Suttie
D000478:Alkylation / Q000187:drug effects; D000595:Amino Acid Sequence; D000645:Ammonium Sulfate / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers; D019735:Carbon-Carbon Ligases; D005170:Factor X / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D008025:Ligases / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011516:Prothrombin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D051381:Rats; D011915:Rats, Inbred BUF / Q000097:blood; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014812:Vitamin K / Q000494:pharmacology; D014859:Warfarin / Q000494:pharmacology
D015415:Biomarkers; D009363:Neoplasm Proteins; D010713:Phosphatidylcholines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014812:Vitamin K; D014859:Warfarin; D011516:Prothrombin; D005170:Factor X; D008025:Ligases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase; D000645:Ammonium Sulfate