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 prolifer ation of the breast cancer cell line Hs578T was investigated. When Hs5 78T cells were depleted of serum their proliferation was drastically r etarded. This was partially counteracted by insulin or IGF-1 but not b y EGF. However, if the activity of HMG-CoA reductase was inhibited, th ere 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 meva lonate, or some of its products, inhibits steps in the EGF signal path way.