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

doi:10.1016/j.molonc.2008.06.004

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 journal › Article › peer-review

20 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 language	English
Pages (from-to)	241-249
Number of pages	9
Journal	Molecular Oncology
Volume	2
Issue number	3
DOIs	https://doi.org/10.1016/j.molonc.2008.06.004
Publication status	Published - Oct 2008

Keywords

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

ASJC Scopus subject areas

Molecular Medicine
Genetics
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.molonc.2008.06.004

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Ueda, N., Shiraha, H., Fujikawa, T., Takaoka, N., Nakanishi, Y., Suzuki, M., Matsuo, N., Tanaka, S., Nishina, S. I., 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, 2(3), 241-249. https://doi.org/10.1016/j.molonc.2008.06.004

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

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

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.",

keywords = "Dominant-negative inhibitor, Prothrombin, Splice variant, Tumor markers, Vitamin K-dependent proteins",

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

note = "Funding Information: We would like to thank Naoki Magario, Keisuke Watanabe, and Toru Naraki (Eisai Co. Ltd., Tokyo, Japan) for the determination of DCP levels. This work was supported by a grant from the Japan Society for the Promotion of Science (Grant Number 16390210).",

year = "2008",

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doi = "10.1016/j.molonc.2008.06.004",

language = "English",

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T1 - Exon 2 deletion splice variant of γ-glutamyl carboxylase causes des-γ-carboxy prothrombin production in hepatocellular carcinoma cell lines

AU - Ueda, Naoki

AU - Shiraha, Hidenori

AU - Fujikawa, Tatsuya

AU - Takaoka, Nobuyuki

AU - Nakanishi, Yutaka

AU - Suzuki, Mayumi

AU - Matsuo, Noriyuki

AU - Tanaka, Shigetomi

AU - Nishina, Shin ichi

AU - Uemura, Masayuki

AU - Takaki, Akinobu

AU - Shiratori, Yasushi

AU - Yamamoto, Kazuhide

N1 - Funding Information: We would like to thank Naoki Magario, Keisuke Watanabe, and Toru Naraki (Eisai Co. Ltd., Tokyo, Japan) for the determination of DCP levels. This work was supported by a grant from the Japan Society for the Promotion of Science (Grant Number 16390210).

PY - 2008/10

Y1 - 2008/10

N2 - 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.

AB - 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.

KW - Dominant-negative inhibitor

KW - Prothrombin

KW - Splice variant

KW - Tumor markers

KW - Vitamin K-dependent proteins

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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