Identification of a repressor of the differentiation of WEHI-3B D- leukemia cells.
The WEHI-3B D+ leukemia is a near-diploid differentiation-competent cell line that undergoes myeloid differentiation in response to retinoic acid. WEHI-3B D- cells, derived from WEHI-3B D+ cells, are near tetraploid and not responsive to the differentiation-inducing properties of the retinoid. To gain information on mechanisms that regulate the maturation of these two cell lines, several multiploid cell lines have been established through fusion of WEHI-3B D+ and WEHI-3B D- cells. Studies with the multiploid cell lines have shown that (a) the cellular growth rate decreases with increased DNA ploidy; (b) near-tetraploid D+/+ cells, obtained by fusing WEHI-3B D+ with WEHI-3B D+ cells, remain differentiation-competent, demonstrating that no direct relationship exists between differentiation competency and DNA ploidy; and (c) near-hexaploid D +/- and D -/+ cells, formed by fusion of WEHI-3B D+ with WEHI-3B D- cells, do not respond to differentiation inducers, suggesting the inhibition of the differentiation machinery of WEHI-3B D+ cells by components from maturation-incompetent WEHI-3B D- cells. The scl transcription factor gene is expressed in WEHI-3B D- cells and is absent in WEHI-3B D+ cells. Overexpression of scl by transfection of scl cDNA in WEHI-3B D+ cells markedly decreased the capacity of retinoic acid to induce differentiation, suggesting that scl functions as a repressor of differentiation in WEHI-3B cell lines.
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
J
J
Li
R A
RA
Finch
W
W
Xiao
A C
AC
Sartorelli
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division; D002459:Cell Fusion; D048429:Cell Size; D002762:Cholecalciferol / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D004171:Diploidy; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology*; D018021:Lithium Chloride / Q000494:pharmacology; D051379:Mice; D011123:Polyploidy; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D051792:Basic Helix-Loop-Helix Proteins; D002762:Cholecalciferol; D004268:DNA-Binding Proteins; D016179:Granulocyte Colony-Stimulating Factor; D018021:Lithium Chloride; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; D014212:Tretinoin; C489366:Tal1 protein, mouse