Interferon alpha induces the expression of retinoblastoma gene product in human Burkitt lymphoma Daudi cells: role in growth regulation.
Interferon alpha (IFN-alpha) is a regulatory secretory protein with distinctive biological effects such as antiproliferative actions against many tumor cell lines, including human Burkitt lymphoma Daudi cells. The mechanism underlying growth inhibition by IFN-alpha is not well established. The growth of many mammalian cell types is also regulated by tumor suppressor retinoblastoma (RB) gene product, the RB protein. In the studies presented here, we explored the possible involvement of RB protein in the growth inhibitory action of IFN-alpha in the Daudi cell model system. We observed that IFN-alpha induces a 3- to 10-fold increased expression of RB protein in growth-sensitive Daudi cells but not in the growth-resistant variant of Daudi cells. IFN-alpha-mediated induction of RB protein was an early event that preceded the period of growth inhibition of Daudi cells. IFN-alpha-induced RB protein predominantly exists as the underphosphorylated form. Addition of antibody against IFN-alpha to Daudi cells resulted in the inhibition of constitutive expression of RB protein and stimulation of [3H]thymidine incorporation. These results demonstrate that the induction of RB protein expression in IFN-alpha-treated Daudi cells could constitute an important mechanism of IFN-alpha-mediated growth regulation.
Kumar
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Laboratory of Receptor Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
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D002051:Burkitt Lymphoma; D002455:Cell Division / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D016161:Genes, Retinoblastoma; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D006131:Growth Inhibitors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein