Phorbol ester reduces number of heparin‐binding growth‐factor receptors in human adult endothelial cells

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Abstract
Heparin-binding growth factors (HBGF) are essential and key mitogens for human adult large vessel endothelial cells. At 170 pg/ml, the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) caused a 50% inhibition of heparin-binding growth factor type one (HBGF-1)-stimulated DNA synthesis in human adult large vessel endothelial cells. TPA at 1 ng/ml completely inhibited HBGF-1-stimulated proliferation. TPA at 5 ng/ml reduced specific HBGF-1 receptor sites from 6600 per cell to 3200 per cell without affecting receptor affinity. Since phorbol esters are potent activators of protein kinase C, these results suggest that activation of protein kinase C desensitizes both animal capillary and human adult large vessel endothelial cells to the mitogenic effects of HBGF by down-regulation of specific HBGF receptors.— Hoshi, H.; Kan, M.; Mioh, H.; Chen, J.-K.; McKeehan, W. L. Phorbol ester reduces number of heparin-binding growth factor receptors in human adult endothelial cells. FASEB J. 2: 2797-2800; 1988.