Differences in thermostability of thymidine kinase isoenzymes in normal ovary and ovarian carcinoma

Citation
A. Demeter et al., Differences in thermostability of thymidine kinase isoenzymes in normal ovary and ovarian carcinoma, ANTICANC R, 21(1A), 2001, pp. 353-358
Citations number
21
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ANTICANCER RESEARCH
ISSN journal
0250-7005 → ACNP
Volume
21
Issue
1A
Year of publication
2001
Pages
353 - 358
Database
ISI
SICI code
0250-7005(200101/02)21:1A<353:DITOTK>2.0.ZU;2-J
Abstract
Thymidine kinase I (TK 1 EC. 2.7.1.21) the most specific and cell-cycle reg ulated salvage enzyme for pyrimidine nucleoside supply of DNA synthesis is a promising target to rationally designed chemo- and other therapies. The p resent study was undertaken to compare the heat stability of TK isoenzymes of both normal and ovarian and epithelial ovarian cancer cells. Tissue extr acts of epithelial ovarian carcinomas (N=7) and normal ovaries (N=9) were a nalyzed for thymidine kinase activity using the polyethyleneimine-cellulose disc radioassay. The TK activity in extracts of ovarian carcinomas was 12- fold higher than in extracts of normal ovaries. The TK activity of ovarian carcinomas decreased significantly even after 30 minutes incubation ar 37 d egreesC while, the enzyme activity of normal ovarian extracts was more stab le and decreased to the same extent after 120 minutes. the half-life time o f the enzyme activy was 82 min in the normal but only 36 minutes in the can cer tissue extract at 37 degreesC. Conclusion: The TK activity of malignant ovarian cells was much higher but more unstable (t(1/2)=36 minutes) than t he enzyme isolated from healthy ovaries (t(1/2)=82 minutes). This profound difference in thermostability might provide the molecular background for hy perthermia combined with chemotherapy as a promising treatment for ovarian malignancies.