Premium
Levels of vitamin K, immunoreactive prothrombin, des‐γ‐carboxy prothrombin and γ‐glutamyl carboxylase activity in hepatocellular carcinoma tissue
Author(s) -
YAMAGATA HIDEHARU,
NAKANISHI TOSHIMI,
FURUKAWA MIDORI,
OKUDA HIROAKI,
OBATA HIROSHI
Publication year - 1995
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.1995.tb01040.x
Subject(s) - hepatocellular carcinoma , prothrombin time , medicine , vitamin , pyruvate carboxylase , endocrinology , microsome , biology , enzyme , biochemistry
To clarify the mechanism of production of des‐γ‐carboxy (abnormal) prothrombin (DCP) by hepatocellular carcinoma (HCC), we measured the levels of vitamin K, DCP, immunoreactive prothrombin and the activity of γ‐glutamyl carboxylase in liver tissues from HCC patients and in the medium of cultured human hepatoma cells. There was no significant difference in vitamin K (K 1 , MK‐4) contents between HCC and non‐HCC cirrhotic liver tissues. The activity of γ‐glutamyl carboxylase per unit amount of endogenous microsomal prothrombin precursor was decreased in HCC tissue compared with non‐HCC liver tissue (positive plasma DCP: 335 ± 72 vs 372 ± 67, negative plasma DCP: 370 ± 84 vs 393 ± 56 nmol/min per mg prothrombin precursor, P > 0.05), although the total incorporation of 14 COOH into microsomal precursor protein was higher in the former. By contrast, levels of DCP and immunoreactive prothrombin in HCC tissue were greater ( P > 0.05) than those in non‐HCC cirrhotic liver tissue. Furthermore, production of large amounts of immunoreactive prothrombin was observed in human hepatoma cells huH‐1 and huH‐2, which produced large amounts of DCP. These results suggest that there was excessive synthesis of prothrombin precursors by human HCC tissue and hepatoma cell lines huH‐1 and huH‐2. Thus, excessive synthesis of prothrombin precursors seems to be the main mechanism of DCP production by HCC.