Vinblastine-dependent down-modulation of TNF receptors in human osteosarcoma cells is mediated by protein kinase C activity.
The binding of tumor necrosis factor (TNF) to a human osteogenic sarcoma cell line (Saos-2) was investigated. These cells express two types of receptors as determined by specific monoclonal antibodies. Vinblastine induced a down-modulation of these receptors weaker than the one produced by phorbol esters or okadaic acid treatment. On exposure of cells to 10 microM vinblastine for two hours an approximately 55-65% diminution of TNF binding was observed, but only 20% reduction occurred under long-term vinblastine treatment. TNF receptor down-modulation induced by vinblastine was partially prevented by protein kinase C inhibitors or protein kinase C depletion. It is suggested that the regulation of TNF binding to each one of its receptors in Saos-2 cells always occurs in a phosphorylation-dependent manner.
Boscoboinik
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Institut für Biochemie und Molekularbiologie, Universität Bern, Switzerland.
Galeotti
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T
Azzi
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A
D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008970:Molecular Weight; D012516:Osteosarcoma / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014747:Vinblastine / Q000494:pharmacology*
D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D014747:Vinblastine; D011493:Protein Kinase C