COOPERATIVE REGULATION OF C-MYC EXPRESSION IN DIFFERENTIATION OF HUMAN PROMYELOCYTIC LEUKEMIA INDUCED BY RECOMBINANT GAMMA-INTERFERON AND 1,25-DIHYDROXYVITAMIN D3

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (9) , 4366-4371
Abstract
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.

This publication has 23 references indexed in Scilit: