Amplified expression of three jun family members inhibits erythroleukemia differentiation.
Several different proto-oncogenes have been shown to influence cellular differentiation. One of the most widely studied model systems has been the Friend murine erythroleukemia cell (F-MELC) line, which can be induced to undergo erythroid differentiation by a variety of chemical agents. Constitutive overexpression of either the c-myc or c-myb proto-oncogenes has been previously shown to inhibit F-MELC differentiation, whereas c-myc antisense sequences accelerate the process. To investigate the potential involvement of other proto-oncogenes and immediate early response genes in F-MELC differentiation, we studied the expression of the three known members of the jun family as well as another gene, egr-1, which, like the jun family members, is expressed as an immediate early response gene in growth factor-stimulated quiescent cells. All four genes were expressed in F-MELC, although the levels of expression and modes of regulation differed. Transfection with amplifiable c-jun, junB, or junD expression plasmids inhibited differentiation, whereas transfection with an egr-1 expression plasmid was without effect. These results indicate that jun family members play a role in mediating F-MELC differentiation. The known inhibitory effect of phorbol ester tumor promoters on F-MELC differentiation may be the result of their known stimulation of jun expression.
Prochownik
E V
EV
Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor.
Smith
M J
MJ
Snyder
K
K
Emeagwali
D
D
D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000235:genetics / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D051766:Early Growth Response Protein 1; D005622:Friend murine leukemia virus; D005784:Gene Amplification / Q000235:genetics*; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D017874:Immediate-Early Proteins; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics* / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D004121:Dimethyl Sulfoxide