Abolition of Mevinolin-induced Growth Inhibition in Human Fibroblasts following Transformation by Simian Virus 40

摘要: The basal level of the gene expression and activity 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase was higher in SV40-transformed human fibroblasts (90-VA VI) than normal ones (HDF). In both these cell types mevinolin (25 µm) caused an 85–90% depression HMG CoA incorporation [3H]acetate into sterols. HDF this coupled to efficient block growth, whereas growth 90-VA VI only slightly reduced by mevinolin. HDF, also abolished essentially all dolichol synthesis, as measured [3H]acetate. contrast, synthesis remained unaltered, or increased, mevinolin-treated VI. We suggest that different responses may depend on substrate affinities rate-limiting enzyme pathway. However, if treated with 25-hydroxycholesterol (25-OH), alternative inhibitor reductase, cellular well significantly decreased. Since inhibitory effect 25-OH did not exceed mevinolin, it seems 25-OH, besides inhibiting inhibits steps distal reductase. This notion further supported finding addition mevalonate prevent 25-OH-induced inhibition. added along partially prevented, indicating a critical de novo is essential for growth.