Lineage-specific regulation of cell cycle gene expression in differentiating myeloid cells.
We have analysed the expression of 7 cyclin and cyclin-associated kinase (cdk) genes in the human myeloid cell line HL-60 at different stages of the cell cycle in non-synchronised cells and during terminal differentiation. A clear cell cycle-dependent expression was found with cyclins A (S+G2), B (G2) and E (late G1 and S), while other cell cycle genes showed only very weak (cdk2) or no periodic expression (cyclin D1, cyclin D2 and cdk4). Induction of macrophage-like differentiation by TPA or granulocytic differentiation by retinoic acid or DMSO was accompanied by a block in G1 and resulted in distinct patterns of gene expression that were lineage- and inducer-specific. These included: (i) a dramatic decrease in the expression of cyclin A, cyclin B and cdk2, and surprisingly an up-regulation of cyclin D1 in TPA-induced macrophage-like cells; (ii) a down-regulation of cyclin E in retinoic acid-induced granulocytic cells; and (iii) a decreased abundance of cyclin D1 and D2, but high levels of cyclin A, B and E RNA in DMSO-induced granulocytic cells. These observations suggest that the mechanisms leading to a differentiation-associated cell cycle arrest are lineage-specific, and that the sustained expression of cyclin and cdk genes does not interfere with the induction of terminal differentiation.
Bürger
C
C
Institut für Molekularbiologie und Tumorforschung (IMT), Philipps-Universität Marburg, Germany.
Wick
M
M
Müller
R
R
D001483:Base Sequence; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis*; D016213:Cyclins / Q000096:biosynthesis*; D017931:DNA Primers; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D012334:RNA, Neoplasm / Q000032:analysis / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016213:Cyclins; D017931:DNA Primers; D012334:RNA, Neoplasm; D014212:Tretinoin; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide