Megakaryocytic differentiation of a leukemic cell line, MC3, by phorbol ester: induction of glycoprotein IIb/IIIa and effects on expression of IL-6, IL-6 receptor, mpl and GATA genes.
We investigated megakaryocytic differentiation in a newly-established Ph1-positive leukemic cell line, MC3, which showed tri-lineage immunophenotypes (myeloid antigens2+, CD19(1+) and CD41a1+) and was positive for CD34 and CD38. TPA induced MC3 cells to differentiate to an early stage of megakaryocyte lineage exhibiting an increase in the expression of platelet glycoproteins (GP) IIb/IIIa (CD41a), and an increase in cell size and nuclear ploidy. TPA treatment also enhanced the expression of GPIIb mRNA, and induced the expression of interleukin-6 (IL-6) and its receptor mRNAs, while it did not induce transcripts of the genes IL-11 and mpl ligand, and further decreased the transcript of the mpl gene. Consistent with these findings, MC3 cells treated with TPA showed an increased expression of GATA-1, but not GATA-3 transcripts, whereas those without TPA treatment expressed only the GATA-2 transcript. These results provide an insight into the study for the regulatory mechanism of megakaryocytopoiesis and leukemic cell differentiation.
Okabe
M
M
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Kunieda
Y
Y
Shoji
M
M
Nakane
S
S
Kurosawa
M
M
Tanaka
J
J
Hansen
S R
SR
Asaka
M
M
D015703:Antigens, CD / Q000378:metabolism*; D001483:Base Sequence; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics*; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008533:Megakaryocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin / Q000378:metabolism*; D019947:Receptors, Interleukin-6; D053628:Receptors, Thrombopoietin; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D015703:Antigens, CD; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D015850:Interleukin-6; D009363:Neoplasm Proteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D053628:Receptors, Thrombopoietin; D014157:Transcription Factors; C082218:MPL protein, human; D013755:Tetradecanoylphorbol Acetate