Exon 2 deletion splice variant of gamma-glutamyl carboxylase causes des-gamma-carboxy prothrombin production in hepatocellular carcinoma cell lines.
Using GGCX gene-specific real-time PCR, exon 2 deletion splice variant of vitamin K-dependent gamma-glutamyl carboxylase (GGCX) mRNA was identified in HCC cell lines. Expressions of wild type and exon 2 deletion variant of GGCX were analyzed with relevance to DCP production in HCC cell lines. Hep3B, HepG2, HuH1, HuH7, and PLC/PRF/5 produced DCP, while SK-Hep-1, HLE, HLF, and JHH1 produced no detectable level of DCP. DCP-producing cells expressed exon 2 deletion variant of GGCX mRNA and protein, while DCP-negative cells expressed no detectable level of exon 2 deletion variant of GGCX. These results suggest that exon 2 deletion splice variant of GGCX causes dysfunction of GGCX enzyme activity resulting in DCP production in HCC cell lines.
Ueda
Naoki
N
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Shiraha
Hidenori
H
Fujikawa
Tatsuya
T
Takaoka
Nobuyuki
N
Nakanishi
Yutaka
Y
Suzuki
Mayumi
M
Matsuo
Noriyuki
N
Tanaka
Shigetomi
S
Nishina
Shin-Ichi
S
Uemura
Masayuki
M
Takaki
Akinobu
A
Shiratori
Yasushi
Y
Yamamoto
Kazuhide
K
D015415:Biomarkers; D019735:Carbon-Carbon Ligases / Q000235:genetics / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D005091:Exons; D014644:Genetic Variation; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000096:biosynthesis*; D011516:Prothrombin / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis
D015415:Biomarkers; D007527:Isoenzymes; D011498:Protein Precursors; D012333:RNA, Messenger; C008208:acarboxyprothrombin; D011516:Prothrombin; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase