Nuclear transcription factor GATA-1 is activated during aclacinomycin-induced erythroid differentiation.
Anthracycline antitumor drugs induce erythroid differentiation of the K562 erythroleukemic cell line at subtoxic concentrations. Aclacinomycin (ACM) stimulates this process by activating the erythroid transcription factor GATA-1, that controls genes involved in hemoglobin biosynthesis. To investigate the implication of GATA-1 in this process, we used a specific anti-GATA-1 polyclonal antibody that we produced in our laboratory. The GATA-1 transcription factor was then monitored during erythroid differentiation induced by aclacinomycin. Here we show that a cellular redistribution and a modification of the phosphorylation state of this transcription factor occurred during ACM-mediated cell differentiation. It suggests that anthracyclines can induce the erythroid differentiation of neoplastic cells by activating the transcription factor GATA-1, probably via its clustering into nuclear foci.
Gillet
Reynald
R
Unité MEDIAN, CNRS FRE 2141, UFR Pharmacie, IFR53, 1, rue du Maréchal-Juin, 51096 Reims cedex, France.
Bobichon
Hélène
H
Trentesaux
Chantal
C
D015250:Aclarubicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000918:Antibody Specificity / Q000235:genetics; D002451:Cell Compartmentation / Q000187:drug effects / Q000235:genetics; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D004920:Erythropoiesis / Q000187:drug effects / Q000235:genetics*; D050982:GATA1 Transcription Factor; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects / Q000235:genetics; D006454:Hemoglobins / Q000096:biosynthesis; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D018613:Microscopy, Confocal; D010744:Phosphoric Monoester Hydrolases / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D006454:Hemoglobins; D014157:Transcription Factors; C011157:aclacinomycins; D015250:Aclarubicin; D010744:Phosphoric Monoester Hydrolases