Orotate phosphoribosyltransferase localizes to the Golgi complex and its expression levels affect the sensitivity to anti-cancer drug 5-fluorouracil
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- HOZUMI Yasukazu
- Department of Anatomy and Cell Biology, Yamagata University School of Medicine
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- TANAKA Toshiaki
- Department of Anatomy and Cell Biology, Yamagata University School of Medicine
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- NAKANO Tomoyuki
- Department of Anatomy and Cell Biology, Yamagata University School of Medicine
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- MATSUI Hirooki
- Department of Otolaryngology, Head and Neck Surgery, Yamagata University School of Medicine
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- NASU Takashi
- Department of Otolaryngology, Head and Neck Surgery, Yamagata University School of Medicine
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- KOIKE Shuji
- Department of Otolaryngology, Head and Neck Surgery, Yamagata University School of Medicine
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- KAKEHATA Seiji
- Department of Otolaryngology, Head and Neck Surgery, Yamagata University School of Medicine
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- ITO Tsukasa
- Department of Otolaryngology, Head and Neck Surgery, Yamagata University School of Medicine
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- GOTO Kaoru
- Department of Anatomy and Cell Biology, Yamagata University School of Medicine
書誌事項
- タイトル別名
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- <b>Orotate phosphoribosyltransferase localizes to the Golgi complex and its expression levels affect the sensitivity to anti-cancer drug 5-fluor</b><b>ouracil </b>
この論文をさがす
抄録
Orotate phosphoribosyltransferase (OPRT) is engaged in de novo pyrimidine synthesis. It catalyzes oronitine to uridine monophosphate (UMP), which is used for RNA synthesis. De novo pyrimidine synthesis has long been known to play an important role in providing DNA/RNA precursors for rapid proliferative activity of cancer cells. Furthermore, chemotherapeutic drug 5-fluorouracil (5-FU) is taken up into cancer cells and is converted to 5-fluoro-UMP (FUMP) by OPRT or to 5-fluoro-dUMP (FdUMP) through intermediary molecules by thymidine phosphorylase. These 5-FU metabolites are misincorporated into DNA/RNA, thereby producing dysfunction of these information processing. However, it remains unclear how the subcellular localization of OPRT and how its variable expression levels affect the response to 5-FU at the cellular level. In this study, immunocytochemical analysis reveals that OPRT localizes to the Golgi complex. Results also show that not only overexpression but also downregulation of OPRT render cells susceptible to 5-FU exposure, but it has no effect on DNA damaging agent doxorubicin. This study provides clues to elucidate the cellular response to 5-FU chemotherapy in relation to the OPRT expression level.
収録刊行物
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- Biomedical Research
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Biomedical Research 36 (6), 403-409, 2015
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