Thymidine kinase in epithelial ovarian cancer: relationship with the other pyrimidine pathway enzymes.
TK is a pyrimidine metabolic pathway enzyme involved in salvage DNA synthesis. What roles TK may play in epithelial ovarian cancer and the relationships between TK and the other pyrimidine pathway enzymes remain unclear. We examined TK1 gene expression by RT-PCR and related it to gene expression of TS, TP and DPD in 69 samples from epithelial ovarian cancer, 8 low-malignant-potential tumors, 16 benign ovarian tumors and 34 normal ovaries. Additionally, cytosolic and serum TK activities were determined by radioenzymatic assay. TK1 gene expression, the ratio of TK1 to TS gene expression, that of TK1 to TP and that of TK1 to DPD were significantly higher in epithelial ovarian cancer than in normal ovaries. In epithelial ovarian cancer, TK1 gene expression correlated with cytosolic and serum TK activities, TS and TP gene expression and the ratio of TP to DPD gene expression. Patients with high-TK1 gene expression had a significantly poorer survival than those with low TK1 gene expression. Combined analysis demonstrated that the relative risk of cancer death for tumors with high TK1, high TS and high TP gene expression was greater than that for tumors with high TK1 gene expression alone. TK1 gene expression together with TS, TP and DPD gene expression may play important roles in influencing the malignant behavior of epithelial ovarian cancer. Combination therapy including TK inhibitor is a possible therapeutic intervention in patients with epithelial ovarian cancer.
Fujiwaki
Ritsuto
R
Department of Obstetrics and Gynecology, Shimane Medical University, Izumo, Japan. fuji39@shimane-med.ac.jp
Hata
Kohkichi
K
Nakayama
Kentaro
K
Moriyama
Masashi
M
Iwanari
Osamu
O
Katabuchi
Hidetaka
H
Okamura
Hitoshi
H
Sakai
Eiichi
E
Miyazaki
Kohji
K
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000069287:Capecitabine; D003600:Cytosol / Q000201:enzymology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D042943:Dihydrouracil Dehydrogenase (NADP); D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000401:mortality; D010053:Ovary / Q000378:metabolism; D010088:Oxidoreductases / Q000096:biosynthesis*; D011379:Prognosis; D011743:Pyrimidines / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013937:Thymidine Kinase / Q000096:biosynthesis*; D013939:Thymidine Phosphorylase / Q000096:biosynthesis*; D013940:Thymidylate Synthase / Q000096:biosynthesis*; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D011743:Pyrimidines; D003841:Deoxycytidine; D000069287:Capecitabine; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D013939:Thymidine Phosphorylase; D013937:Thymidine Kinase; D005472:Fluorouracil