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Updated: Aug 12, 2026
Generation of Induced Pluripotent Stem Cells by Reprogramming Human Fibroblasts with the Stemgent Human TF Lentivirus Set
Published on: December 8, 2009
Effect of virus-transformation and growth factor stimulation on isoprene biosynthesis in human fibroblasts: a
1Department of Tumor Pathology, Karolinska Hospital, Stockholm, Sweden.
Abstract:
Serum depletion of exponentially growing normal human fibroblasts resulted in a moderate depression of the activity of HMG-CoA reductase which occurred simultaneously to the onset of growth arrest of the cells. Specific inhibition of HMG-CoA reductase using mevinolin also resulted in growth arrest. PDGF counteracted the suppressive effect of serum depletion on HMG-CoA reductase activity and cell growth. The growth inhibitory effect of serum depletion and mevinolin was correlated to a decreased biosynthesis of dolichols, in particular of dolichol-20. If PDGF was present in the serum-free medium a high rate of dolichol synthesis was maintained. This effect was mediated not only through an increased HMG-CoA reductase activity. PDGF also increased the incorporation of mevalonate into dolichols, once again into dolichol-20 in particular. In contrast to HDF, the growth of virus-transformed human fibroblasts was not decreased following serum depletion. This was correlated to a sustained activity of HMG-CoA reductase and a sustained dolichol-20 synthesis. In order to block growth and dolichol synthesis of the transformed fibroblasts a stronger inhibition of HMG-CoA reductase activity was required than in the normal cells. Conditioned medium isolated from the transformed cells was found to maintain a high growth rate and a high HMG-CoA reductase activity in serum-depleted HDF. In addition, the incorporation of mevalonate into dolichols was increased. The present data raise the possibility that PDGF or related factors, through autocrine loops, may contribute to the maintenance of a high dolichol synthesis in tumor cells.
Insights
Serum depletion halts normal cell growth by reducing HMG-CoA reductase activity and dolichol synthesis. Platelet-derived growth factor (PDGF) prevents this arrest, suggesting its role in maintaining cell growth and dolichol production, especially in tumor cells.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Cellular growth is highly dependent on metabolic pathways.
- HMG-CoA reductase is a key enzyme in cholesterol and isoprenoid biosynthesis.
- Dolichols are essential for protein glycosylation and cell membrane integrity.
Purpose of the Study:
- To investigate the role of HMG-CoA reductase and dolichol synthesis in normal and transformed human fibroblast growth.
- To determine the effect of serum depletion and platelet-derived growth factor (PDGF) on these pathways.
- To explore potential autocrine mechanisms in tumor cell proliferation.
Main Methods:
- Serum depletion of normal human fibroblasts (HDF) and virus-transformed fibroblasts.
- Inhibition of HMG-CoA reductase using mevinolin.
- Measurement of HMG-CoA reductase activity and dolichol biosynthesis.
- Analysis of PDGF effects on cell growth and metabolic pathways.
Main Results:
- Serum depletion moderately decreased HMG-CoA reductase activity and dolichol-20 synthesis, leading to growth arrest in normal fibroblasts.
- PDGF counteracted these effects, maintaining cell growth and dolichol synthesis.
- Transformed fibroblasts showed sustained HMG-CoA reductase activity and dolichol synthesis, resisting serum depletion-induced growth arrest.
- Conditioned medium from transformed cells promoted growth and HMG-CoA reductase activity in serum-depleted normal cells.
Conclusions:
- HMG-CoA reductase activity and dolichol-20 synthesis are critical for normal fibroblast growth.
- PDGF plays a significant role in regulating these pathways and preventing growth arrest.
- Tumor cells may utilize autocrine PDGF signaling to maintain high dolichol synthesis and sustained proliferation.
