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Dihydropyrimidine dehydrogenase in normal and malignant endometrium: relationship with cell proliferation and thymidine phosphorylase

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Abstract

Dihydropyrimidine dehydrogenase (DPD) is a pyrimidine salvage enzyme responsible for degradation of thymine, which is produced from thymidine by thymidine phosphorylase (TP). Our purpose was to determine the relationship between DPD, cell proliferation and TP expression in human endometrium. We examined DPD gene expression using reverse transcription-polymerase chain reaction, DPD protein levels using enzyme-linked immunosorbent assay, and DPD protein localization using immunohistochemistry in 58 normal endometria and 28 endometrial cancers. DPD gene expression was then related to the proliferating cell nuclear antigen index and to TP gene expression. DPD gene expression, which was correlated with DPD protein level, was relatively stable throughout various menstrual phases but was significantly elevated in postmenopausal status. It was significantly lower in endometrial cancer than in normal endometrium. Localization analysis revealed that DPD protein was located primarily in epithelial cells, but was also present in stromal cells. DPD gene expression correlated inversely with the PCNA index. TP gene expression pattern contrasted with that of DPD in postmenopausal and malignant endometrium. A high ratio of TP to DPD gene expression was significantly more frequent in endometrial cancer than in normal endometrium in any menstrual phase. DPD may act cooperatively with TP to affect cell function by maintaining the pyrimidine nucleotide pool balance in normal and malignant endometrium.

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Acknowledgements

This work was supported by a Grant-in-Aid (No. 13770917) from the Japan Society for the Promotion of Science. We thank Mr. Mikio Koike, Laboratory Medicine and Central Clinical Laboratory, Shimane Medical University, for providing paraffin-embedded tissues and Miss Taeko Yamada, Department of Obstetrics and Gynecology, Shimane Medical University, for her management of medical records.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Shimane Medical University, 693-8501, Izumo , Japan

    Ritsuto Fujiwaki, Kohji Iida, Kentaro Nakayama, Haruhiko Kanasaki, Tomoya Ozaki, Kohkichi Hata & Kohji Miyazaki

  2. Nihon Gene Research Lab's Inc., Sendai, Japan

    Eiichi Sakai

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  1. Ritsuto Fujiwaki
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  2. Kohji Iida
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  3. Kentaro Nakayama
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  7. Eiichi Sakai
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  8. Kohji Miyazaki
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Correspondence to Ritsuto Fujiwaki.

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Fujiwaki, R., Iida, K., Nakayama, K. et al. Dihydropyrimidine dehydrogenase in normal and malignant endometrium: relationship with cell proliferation and thymidine phosphorylase. Virchows Arch 443, 672–677 (2003). https://doi.org/10.1007/s00428-003-0866-3

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  • DOI: https://doi.org/10.1007/s00428-003-0866-3

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