Modulation of the c-myb, c-myc and p53 mRNA and protein levels during induced murine erythroleukemia cell differentiation.
The induction of murine erythroleukemia cells (MELC) to terminal differentiation by hexamethylene bisacetamide (HMBA) is accompanied by changes in the levels of c-myb and c-myc mRNA, and in p53 protein levels. We simultaneously examined the effects of HMBA on modulation of c-myb, c-myc and p53 mRNA and protein levels, and examined the relationship between these changes and commitment to terminal cell division. In MELC cultured with HMBA, c-myb protein levels paralleled c-myb mRNA levels except at 24h, when the protein level was equivalent to the level in control cultures, whereas the mRNA had decreased. The c-myc protein paralleled c-myc mRNA throughout induction. The p53 mRNA and protein behaved in a discordant fashion. The p53 protein decreased to very low levels between 4 and 8 h and remained low, while the mRNA, which initially decreased, reaccumulated by 24 and 48 h. Transfer of MELC after 12 to 48 h of culture with HMBA to medium without inducer resulted in rapid (less than 3 h) reaccumulation of the c-myb mRNA, c-myb protein, and p53 protein, and cessation of recruitment of cells to commitment. Cells already induced to commit to terminal differentiation continued to express the differentiated phenotype.
Richon
V M
VM
The DeWitt Wallace Research Laboratory, Memorial Sloan-Kettering Cancer Center, Cornell University, New York, NY 10021.
Ramsay
R G
RG
Rifkind
R A
RA
Marks
P A
PA
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D010750:Phosphoproteins / Q000032:analysis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger / Q000032:analysis*; D016159:Tumor Suppressor Protein p53
D000081:Acetamides; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D003907:Dexamethasone; C014026:hexamethylene bisacetamide