Inhibitory effect of mevalonate on the EGF mitogenic signaling pathway in human breast cancer cells in culture

Cancer Biochem Biophys. 1994 Oct;14(3):193-200.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms
  • Cell Division / drug effects
  • Cell Line
  • Culture Media, Serum-Free
  • Epidermal Growth Factor / pharmacology*
  • Epidermal Growth Factor / physiology
  • ErbB Receptors / biosynthesis
  • ErbB Receptors / metabolism
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Insulin / pharmacology
  • Insulin-Like Growth Factor I / pharmacology
  • Kinetics
  • Lovastatin / pharmacology
  • Mevalonic Acid / pharmacology*
  • Signal Transduction / drug effects*
  • Transcription, Genetic
  • Transforming Growth Factor alpha / pharmacology
  • Tumor Cells, Cultured

Substances

  • Culture Media, Serum-Free
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Insulin
  • Transforming Growth Factor alpha
  • Epidermal Growth Factor
  • Insulin-Like Growth Factor I
  • Lovastatin
  • ErbB Receptors
  • Mevalonic Acid