Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined the interaction of dexamethasone with the ZR75-1 human breast cancer cell line to determine if glucocorticoids might directly inhibit growth of breast cancer cells. Growth of these cells in serum-free medium was stimulated significantly by physiological concentrations of insulin (0.1 to 1.0 nM). Pharmacological concentrations of dexamethasone (10 nM) reduced cell number below that found in controls and nearly abolished the effect of insulin after several days in culture. Thymidine and uridine, but not leucine, incorporation into macromolecules or acetate incorporation into fatty acids were similarly inhibited by dexamethasone in the presence of absence of insulin. Dexamethasone did not inhibit insulin effects by altering insulin receptor affinity or concentration, as determined by Scatchard analyses of insulin binding. Net thymidine uptake into the trichloroacetic acid-soluble fraction of the cell was stimulated by insulin and inhibited by dexamethasone also inhibited thymidine kinase activity multiple potential sites of glucocorticoid action that directly oppose the effects of insulin. They also suggest that glucocorticoids have a direct inhibitory effect on proliferation of human breast cancer cells, which may help explain breast tumor regression following pharmacological glucocorticoid therapy.
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PMID:Direct inhibition of growth and antagonism of insulin action by glucocorticoids in human breast cancer cells in culture. 44 41

We have shown previously that a 500-bp region of the human insulin receptor promoter (-0.3 to -1.8 kb) was able to stimulate transcription from a heterologous thymidine kinase promoter in HepG2 hepatoma cells but not in HeLa fibroblasts. Footprint analysis localized the transcription factor binding sites to a 36-bp region at -1420. In this paper, we analyze the factors that recognize this element and show that it contains binding sites for the CAAT/enhancer binding protein C/EBP and nuclear factor 1 (NF-1). In addition we show that both C/EBP alpha and the C/EBP beta can transactivate the human insulin receptor promoter in a dose-dependent manner.
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PMID:An upstream element from the human insulin receptor gene promoter contains binding sites for C/EBP beta and NF-1. 828 55