Altered expression of cell cycle related genes including c-myb in a subclone of HL-60 that exhibits reversible differentiation.
A differentiation resistant subclone of HL-60, DMSOr, was removed from the selective pressure of dimethyl sulfoxide and characterized with a new stable phenotype of reversible differentiation. DMSOr cells, when treated with 1.25% dimethyl sulfoxide, differentiated in a manner similar to the parental HL-60 with respect to morphological changes, increase in superoxide production, and withdrawal from cell cycle. Upon removal of the dimethyl sulfoxide at points normally associated with commitment to terminal differentiation, DMSOr reverted to the immature phenotype. This demonstrates an uncoupling of the morphological, functional, and antiproliferative effects of differentiation from commitment to terminal differentiation. Associated with the reversible phenotype of DMSOr was an altered expression of the c-myb oncogene. In HL-60, c-myb expression was down-regulated by 72 h and completely diminished by 144 h. Northern blot analysis of DMSOr demonstrated greater levels of expression of c-myb at 72 and 144 h. Similar results were shown with histone H4, cdc2 kinase, and, to a lesser extent, ornithine decarboxylase. The c-myb related gene B-myb did not show altered regulation during differentiation. The results suggest that altered expression of genes that control cell cycle may be critical for the reversible phenotype of DMSOr.
Boise
L H
LH
Department of Pharmacology/Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Grant
S
S
Westin
E H
EH
D001483:Base Sequence; D015152:Blotting, Northern; D002453:Cell Cycle / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002999:Clone Cells / Q000187:drug effects; D004121:Dimethyl Sulfoxide; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D011519:Proto-Oncogenes / Q000235:genetics*; D013481:Superoxides / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D013481:Superoxides; D013936:Thymidine; D004121:Dimethyl Sulfoxide