Cooperative regulation of c-myc expression in differentiation of human promyelocytic leukemia induced by recombinant gamma-interferon and 1,25-dihydroxyvitamin D3.
The biological activity of recombinant human gamma-interferon (IFN-gamma) to induce the phenotypic differentiation of human promyelocytic leukemia cell line HL-60 and to regulate c-myc expression was evaluated. Treatment with IFN-gamma increased monocyte-associated cell surface antigens detected by monocyte-specific monoclonal antibodies in a dose- and time-dependent manner. These antigenic changes were accompanied by a functional differentiation, determined by the increase of phagocytic capability and superoxide generation. IFN-gamma was also found to suppress the growth of HL-60 cells and reduce expression of a c-myc oncogene. These phenotypic and morphological changes to macrophage-like cells induced by IFN-gamma were similar to those by 1,25-dihydroxyvitamin D3, whereas the plasma membrane antigenic changes were different. Moreover, the combination of IFN-gamma and suboptimal doses of 1,25-dihydroxyvitamin D3 have synergistic effects in augmenting mature monocyte specific antigens (Mo2, 63D3, OKM1, and OKM5). In the reduction of c-myc expression by these drugs, a cooperative effect was observed with the inhibition of transferrin receptor expression and cell growth. These results indicate that human recombinant IFN-gamma induces a monocyte phenotype in the HL-60 cells via a mechanism different from the action of 1,25-dihydroxyvitamin D3.
D000954:Antigens, Surface / Q000032:analysis; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology*; D009000:Monocytes / Q000276:immunology; D009857:Oncogenes; D010641:Phenotype
D000954:Antigens, Surface; D007371:Interferon-gamma; D002117:Calcitriol