Exon 2 deletion splice variant of γ-glutamyl carboxylase causes des-γ-carboxy prothrombin production in hepatocellular carcinoma cell lines

Naoki Ueda, Hidenori Shiraha, Tatsuya Fujikawa, Nobuyuki Takaoka, Yutaka Nakanishi, Mayumi Suzuki, Noriyuki Matsuo, Shigetomi Tanaka, Shin ichi Nishina, Masayuki Uemura, Akinobu Takaki, Yasushi Shiratori, Kazuhide Yamamoto

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Using GGCX gene-specific real-time PCR, exon 2 deletion splice variant of vitamin K-dependent γ-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.

Original languageEnglish
Pages (from-to)241-249
Number of pages9
JournalMolecular Oncology
Volume2
Issue number3
DOIs
Publication statusPublished - Oct 2008

Fingerprint

Prothrombin
Hepatocellular Carcinoma
Exons
Cell Line
Messenger RNA
Real-Time Polymerase Chain Reaction
glutamyl carboxylase
Enzymes
Genes
Proteins

Keywords

  • Dominant-negative inhibitor
  • Prothrombin
  • Splice variant
  • Tumor markers
  • Vitamin K-dependent proteins

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Medicine

Cite this

Exon 2 deletion splice variant of γ-glutamyl carboxylase causes des-γ-carboxy prothrombin production in hepatocellular carcinoma cell lines. / Ueda, Naoki; Shiraha, Hidenori; Fujikawa, Tatsuya; Takaoka, Nobuyuki; Nakanishi, Yutaka; Suzuki, Mayumi; Matsuo, Noriyuki; Tanaka, Shigetomi; Nishina, Shin ichi; Uemura, Masayuki; Takaki, Akinobu; Shiratori, Yasushi; Yamamoto, Kazuhide.

In: Molecular Oncology, Vol. 2, No. 3, 10.2008, p. 241-249.

Research output: Contribution to journalArticle

Ueda, N, Shiraha, H, Fujikawa, T, Takaoka, N, Nakanishi, Y, Suzuki, M, Matsuo, N, Tanaka, S, Nishina, SI, Uemura, M, Takaki, A, Shiratori, Y & Yamamoto, K 2008, 'Exon 2 deletion splice variant of γ-glutamyl carboxylase causes des-γ-carboxy prothrombin production in hepatocellular carcinoma cell lines', Molecular Oncology, vol. 2, no. 3, pp. 241-249. https://doi.org/10.1016/j.molonc.2008.06.004
Ueda, Naoki ; Shiraha, Hidenori ; Fujikawa, Tatsuya ; Takaoka, Nobuyuki ; Nakanishi, Yutaka ; Suzuki, Mayumi ; Matsuo, Noriyuki ; Tanaka, Shigetomi ; Nishina, Shin ichi ; Uemura, Masayuki ; Takaki, Akinobu ; Shiratori, Yasushi ; Yamamoto, Kazuhide. / Exon 2 deletion splice variant of γ-glutamyl carboxylase causes des-γ-carboxy prothrombin production in hepatocellular carcinoma cell lines. In: Molecular Oncology. 2008 ; Vol. 2, No. 3. pp. 241-249.
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