Differentiation of mouse erythroleukemia cells is blocked by late up-regulation of a c-myb transgene.
During chemically induced differentiation of Friend virus-infected mouse erythroleukemia (MEL) cell lines, there is a biphasic down-regulation of the c-myb proto-oncogene. A plasmid containing a murine c-myb cDNA controlled by a mouse metallothionein I promoter was transfected into the C19 MEL cell line. For six transfected clones, it was found that expression of the exogenous c-myb mRNA could be up-regulated by the addition of 120 microM ZnCl2 and that the N,N'-hexamethylenebisacetamide-induced differentiation of these transfectants was inhibited in proportion to the level of exogenous c-myb mRNA expression. By adding or removing ZnCl2 at different times during the induction process, it was possible to show that up-regulation of exogenous c-myb limited to the first 2 days of induction had little or no effect on differentiation. In contrast, continuous expression of exogenous c-myb beginning at any time during the period of induction blocked further differentiation. These results suggest that during HMBA induction of MEL cells, the early down-regulation of c-myb mRNA is not necessary for terminal differentiation, whereas the down-regulation of c-myb at a later time is necessary.
McClinton
D
D
NCI-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland 20814.
Stafford
J
J
Brents
L
L
Bender
T P
TP
Kuehl
W M
WM
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002712:Chlorides / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb; D011519:Proto-Oncogenes; D012334:RNA, Neoplasm / Q000235:genetics; D015183:Restriction Mapping; D014162:Transfection; D015032:Zinc / Q000494:pharmacology; D017967:Zinc Compounds
D002712:Chlorides; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D012334:RNA, Neoplasm; D017967:Zinc Compounds; C016837:zinc chloride; D008668:Metallothionein; D011505:Protein-Tyrosine Kinases; D015032:Zinc