Evidence for distinct regulation processes in the aclacinomycin- and doxorubicin-mediated differentiation of human erythroleukemic cells.
Fiche publication
Date publication
mars 1996
Journal
Biochemical pharmacology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LAHLIL Rachid
Tous les auteurs :
Morceau F, Aries A, Lahlil R, Devy L, Jardillier JC, Jeannesson P, Trentesaux C
Lien Pubmed
Résumé
Human erythroleukemic K 562 cells were induced to were induced to differentiate along the erythroid lineage by anthracycline antitumor drugs, such as aclacinomycin (ACLA) and doxorubicin (DOX). Subsequent stimulation of heme and globin synthesis led to a differential quantitative expression of hemoglobins. Gower 1 (epsilon2, zeta2) was the major type for ACLA and X (epsilon2, gamma2) for DOX. Although ACLA and DOX increased both the expression of gamma-globin and porphobilinogen deaminase mRNAs, striking differences were observed in the expression of erythropoietin receptor mRNAs and in erythroid transcription factors GATA-1 and NF-E2, known to play a key role in erythroid gene regulation. Indeed, ACLA induces an increase either in the binding capacity of GATA-1 and NF-E2 or in the accumulation of erythropoietin receptor, GATA-1 and NF-E2 transcripts. In contrast, their expression with DOX was not significantly modified compared to uninduced cells, except for a slight decrease in NF-E2 expression on day 3. In conclusion, these data show that: 1. increased expression of erythroid transcription factors and erythroid genes are associated only with ACLA treatment, and 2. although cytotoxicity of both ACLA and DOX is certainly dependent on DNA intercalation, regulation of differentiation processes by these two drugs involves distinct mechanisms.
Mots clés
Aclarubicin, analogs & derivatives, Antibiotics, Antineoplastic, pharmacology, Base Sequence, Cell Differentiation, drug effects, DNA-Binding Proteins, biosynthesis, Doxorubicin, pharmacology, Erythroid-Specific DNA-Binding Factors, GATA1 Transcription Factor, Gene Expression, drug effects, Globins, biosynthesis, Hemoglobins, biosynthesis, Humans, Hydroxymethylbilane Synthase, biosynthesis, Leukemia, Erythroblastic, Acute, drug therapy, Molecular Sequence Data, NF-E2 Transcription Factor, NF-E2 Transcription Factor, p45 Subunit, RNA, Messenger, genetics, Receptors, Erythropoietin, biosynthesis, Transcription Factors, biosynthesis, Tumor Cells, Cultured
Référence
Biochem. Pharmacol.. 1996 Mar;51(6):839-45