Regulation of gene expression by tumor promoters. II. Control of cell shape and developmental programs for macrophages and granulocytes in human myeloid leukemic cells

✍ Scribed by Dan Liebermann; Barbara Hoffman-Liebermann; Leo Sachs

• Publisher: John Wiley and Sons
• Year: 1981
• Tongue: French
• Weight: 769 KB
• Volume: 28
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910280306

✦ Synopsis

Abstract

Regulation of the developmental programs for macrophages and granulocytes has been analysed, using two‐dimensional gel electrophorels of the cytoplasmic protein changes, in a human myeloid leukemic cell line (HL60) that can be induced to differentiate to macrophages by the macrophage and granulocyte‐inducing (MGI) protein and the tumor promoter 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA), and to granulocytes by dimethylsulfoxide (DMSO). Studies on the protein changes induced by the different inducers showed a similar developmental program for macrophage differentiation induced by MGI or TPA, which differed from the beginning from the granulocyte program induced by DMSO. Comparison with normal cells from human peripheral blood has shown that the developmental programs induced in the HL60 cells are relevant to the normal programs of differentiation for these two cell types. Unlike MGI and DMSO, TPA induces rapid attachment of the HL60 cells to the surface of the Petri dish. Combined treatment with TPA and DMSO showed cell attachment, extensive spreading of the cells, the regulation of specific proteins and expression of the macrophage program. The addition of TPA to cells induced for the granulocyte program by DMSO resulted in cell attachment and spreading and a switchover from the granulocyte to the macrophage program. The results indicate that cells in suspension can express either the macrophage or granulocyte program depending on the inducer, and that changes in cell shape associated with cell attachment induced by TPA can regulate specific proteins and restrict the developmental program to macrophages. It is suggested that the in vivo environment of cells in relation to the possibilities for cell adhesion, which can be regulated by tumor promotors, may play a major role in determining the developmental program of myeloid and other cell types.