Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alkylation / drug effects
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Amino Acid Sequence
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Ammonium Sulfate / pharmacology
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Animals
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Biomarkers
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Carbon-Carbon Ligases*
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Factor X / pharmacology
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Gene Expression Regulation, Neoplastic
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Ligases / metabolism*
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Liver Neoplasms, Experimental / metabolism
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Liver Neoplasms, Experimental / pathology
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Male
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Molecular Sequence Data
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Phosphatidylcholines / pharmacology
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Protein Processing, Post-Translational* / drug effects
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Prothrombin / biosynthesis
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Prothrombin / genetics
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Prothrombin / metabolism*
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RNA, Messenger / genetics
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RNA, Neoplasm / genetics
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Rats
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Rats, Inbred BUF / blood
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Tumor Cells, Cultured / drug effects
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Vitamin K / pharmacology
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Warfarin / pharmacology
Substances
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Biomarkers
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Neoplasm Proteins
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Phosphatidylcholines
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RNA, Messenger
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RNA, Neoplasm
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Vitamin K
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Warfarin
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Prothrombin
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Factor X
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Ligases
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Carbon-Carbon Ligases
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glutamyl carboxylase
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Ammonium Sulfate