Changes in c-myc, c-fms, and N-ras proto-oncogene expression associated with retinoic acid-induced monocytic differentiation of human leukemia HL60/MRI cells.

The human promyelocytic leukemia cell line HL60 differentiates to granulocytic cells when treated with retinoic acid (RA). In contrast, HL60/MRI, a cell line established from a transplantable HL60 tumor in nude mice, differentiates to monocytoid cells in response to RA (M. Imaizumi, J. Uozumi, and T. R. Breitman, Cancer Res., 47: 1434-1440, 1987). Because alterations of proto-oncogene expression may be closely related to the difference in response of HL60/MRI to RA we studied the expression of the proto-oncogenes myc, fms, and N-ras of HL60/MRI in comparison to HL60. Compared to HL60, the proto-oncogene myc of HL60/MRI is amplified about twofold less in genomic DNA and is expressed about twofold less at the transcriptional level. Even though two subclones of HL60/MRI, 28B.4 and 5B, have about the same steady-state levels of c-myc mRNA before treatment with RA, 28B.4 has a more rapid decrease of c-myc mRNA after treatment with RA. Based on two differentiation markers, nitro blue tetrazolium reduction and the OKM-5 monocyte-specific surface antigen, 28B.4 exhibits a greater response to RA than does 5B. c-fms mRNA is not detected in uninduced HL60/MRI and HL60 but is expressed during RA-induced differentiation of HL60/MRI to monocytes/macrophages and HL60 to granulocytes. The expression of N-ras mRNA of 5B decreases about twofold during the first 12 h of exposure to RA and is then relatively constant for another 36 h.