Induction of differentiation in Friend-erythroleukemia cells by aclacinomycin A: early transient decrease in c-myc and c-myb mRNA levels.
Chemical inducers of the differentiation are known to cause an early transient decrease in c-myc and c-myb mRNA levels in Friend erythroleukemia cells preceding the down-regulation of c-myc and c-myb expression in the course of irreversible terminal differentiation. We therefore investigated the early effect of the potent differentiation-inducing anthracycline antitumor antibiotic, aclacinomycin A, on the c-myc and c-myb mRNA levels in the Friend cell line, F4-6, using Northern blot analysis. Aclacinomycin A induced a rapid decrease in the levels of c-myc and c-myb transcripts within 0.5-1 h and 2-3 h, respectively. The time course of decline in c-myc and c-myb expression was similar to that observed with dimethylsulfoxide or after transcription blockage brought about by a high concentration of actinomycin D. By 12 to 18 h after aclacinomycin A exposure, the c-myc and c-myb mRNA levels had returned to about pretreatment levels. When the cells were treated with adriamycin, an anthracycline that reduces cell proliferation in F4-6 cells without increasing differentiation, an early decrease in c-myc and c-myb expression was not observed. These results suggest that the transient decrease in c-myc and c-myb mRNA levels in F4-6 cells may be an early differentiation-related biochemical effect of aclacinomycin A.
Schaefer
A
A
Department of Toxicology, University of Hamburg Medical School, Germany.
Dressel
A
A
Lingelbach
K
K
Schmidt
C A
CA
Steinheider
G
G
Marquardt
H
H
D015250:Aclarubicin / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005622:Friend murine leukemia virus; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects*; D006454:Hemoglobins / Q000096:biosynthesis; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009857:Oncogenes / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D006454:Hemoglobins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015250:Aclarubicin; D004317:Doxorubicin; D004121:Dimethyl Sulfoxide