Increased activities of thymidylate synthetase and thymidine kinase in human thyroid tumors.
Thymidylate synthetase (TS) is known to catalyse the methylation of deoxyuridine monophosphate (dUMP) for the de novo synthesis of deoxythymidine monophosphate (dTMP). Thymidine kinase (TK) catalyzes the formation of dTMP by the phosphorylation of thymidine via the pyrimidine salvage pathway. High TS and TK activities have been observed in rapidly proliferating tissues. Both TS and TK activities in human thyroid adenocarcinoma increased to approximately 2-fold that in normal thyroid tissue. The thyroid TK isozymes can be separated into two types by DEAE-cellulose column chromatography. One of them is associated with the cytosol cell fraction of rapidly proliferating cells, such as fetal or neoplastic cells. Its activity is not affected by low concentration of deoxycytidine triphosphate (dCTP), and its molecular weight and Km value for thymidine are 120 kD and 0.5 x 10(-6) M, respectively. The average activity of this cytosol-associated isozyme in thyroid adenocarcinoma was increased slightly to 2.3-fold that of normal thyroid tissue. These results obtained from the activities of TK and its isozyme may be indicative of the slow-growing property of thyroid adenocarcinoma compared to mammary or colonic adenocarcinoma, which has high activities of TK and its isozyme.
Sakamoto
S
S
Medical Research Institute, Tokyo Medical and Dental University, Japan.
Murakami
S
S
Sugawara
M
M
Mishima
Y
Y
Okamoto
R
R
D000230:Adenocarcinoma / Q000201:enzymology*; D000236:Adenoma / Q000201:enzymology*; D000328:Adult; D002848:Chromatography, DEAE-Cellulose; D003570:Cytidine Triphosphate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D008875:Middle Aged; D013937:Thymidine Kinase / Q000096:biosynthesis*; D013940:Thymidylate Synthase / Q000096:biosynthesis*; D013942:Thymine Nucleotides / Q000494:pharmacology; D013961:Thyroid Gland / Q000201:enzymology; D013964:Thyroid Neoplasms / Q000201:enzymology*
D007527:Isoenzymes; D013942:Thymine Nucleotides; D003570:Cytidine Triphosphate; D013940:Thymidylate Synthase; D013937:Thymidine Kinase; C024157:thymidine 5'-triphosphate