Inhibitory effect of mevalonate on the EGF mitogenic signaling pathway in human breast cancer cells in culture.
The relationship between the effects of EGF and mevalonate on proliferation of the breast cancer cell line Hs578T was investigated. When Hs578T cells were depleted of serum their proliferation was drastically retarded. This was partially counteracted by insulin or IGF-1 but not by EGF. However, if the activity of HMG-CoA reductase was inhibited, there was a significant increase in DNA synthesis of EGF-treated cells. This effect was not seen in cells stimulated by insulin or IGF-1, and was prevented by addition of mevalonate. The results suggest that mevalonate, or some of its products, inhibits steps in the EGF signal pathway.
Larsson
O
O
Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
Blegen
H
H
D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016895:Culture Media, Serum-Free; D004815:Epidermal Growth Factor / Q000494:pharmacology* / Q000502:physiology; D066246:ErbB Receptors / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007700:Kinetics; D008148:Lovastatin / Q000494:pharmacology; D008798:Mevalonic Acid / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016895:Culture Media, Serum-Free; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D008148:Lovastatin; D066246:ErbB Receptors; D008798:Mevalonic Acid