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Increased thymidylate synthase (EC 2.1.1.45) activity in normal and neoplastic proliferation
Y Hashimoto1, T Shiotani, J N Eble
1Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis 46223.
Cancer Biochemistry Biophysics
|July 1, 1988
Summary
Thymidylate synthase (dTMP) activity is low in normal adult rat liver but high in rapidly proliferating tissues. This enzyme
Area of Science:
- Biochemistry
- Enzymology
- Molecular Biology
Background:
- Thymidylate synthase (dTMP) is crucial for DNA synthesis.
- Its activity varies significantly across different tissues and developmental stages.
- Elevated dTMP synthase activity is implicated in various cancers.
Purpose of the Study:
- To quantify thymidylate synthase (dTMP) activity in various rat tissues.
- To investigate the correlation between dTMP synthase activity and proliferation rates in rat hepatomas.
- To assess dTMP synthase activity in human colon carcinomas and leukemic leukocytes.
Main Methods:
- A sensitive and rapid radioassay was employed to measure dTMP synthase activity.
- Enzyme activity was determined in 100,000 x g supernatant fractions.
- Comparisons were made between normal tissues, developing tissues, and cancerous tissues.
Main Results:
- Normal adult rat liver exhibited low dTMP synthase activity.
- Rat thymus, spleen, and bone marrow showed significantly higher dTMP synthase activity compared to liver.
- dTMP synthase activity was markedly elevated in rat hepatomas, human colon carcinomas, and leukemic leukocytes, correlating with proliferation rates.
Conclusions:
- Thymidylate synthase (dTMP) activity is highly regulated and tissue-specific.
- Increased dTMP synthase expression is a hallmark of rapidly proliferating cells and cancers.
- This enzyme represents a potential therapeutic target in oncology.