Dihydropyrimidine dehydrogenase in normal and malignant endometrium: relationship with cell proliferation and thymidine phosphorylase.
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.
Fujiwaki
Ritsuto
R
Department of Obstetrics and Gynecology, Shimane Medical University, 693-8501, Izumo, Japan. fuji39@shimane-med.ac.jp
Iida
Kohji
K
Nakayama
Kentaro
K
Kanasaki
Haruhiko
H
Ozaki
Tomoya
T
Hata
Kohkichi
K
Sakai
Eiichi
E
Miyazaki
Kohji
K
D002455:Cell Division / Q000502:physiology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000502:physiology*; D016889:Endometrial Neoplasms / Q000201:enzymology*; D004717:Endometrium / Q000166:cytology / Q000201:enzymology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008597:Menstrual Cycle / Q000502:physiology; D017698:Postmenopause / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013939:Thymidine Phosphorylase / Q000502:physiology*
D018809:Proliferating Cell Nuclear Antigen; D042943:Dihydrouracil Dehydrogenase (NADP); D013939:Thymidine Phosphorylase