title: Down-regulation of a serine protease, myeloblastin, causes growth arrest and differentiation of promyelocytic leukemia cells.
abstract: Cells from the human leukemia cell line HL-60 undergo terminal differentiation when exposed to inducing agents. Differentiation of these cells is always accompanied by withdrawal from the cell cycle. Here we describe the isolation of a cDNA encoding a novel serine protease that is present in HL-60 cells and is down-regulated during induced differentiation of these cells. We have named this protease myeloblastin. Down-regulation of myeloblastin mRNA occurs with both monocytic and granulocytic inducers. Myeloblastin mRNA is undetectable in fully differentiated HL-60 cells as well as in human peripheral blood monocytes. We found that regulation of myeloblastin mRNA in HL-60 cells is serum dependent. Inhibition of myeloblastin expression by an antisense oligodeoxynucleotide inhibits proliferation and induces differentiation of promyelocyte-like leukemia cells.
authors.affiliation: Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York 10032.
authors.forename: D
authors.initials: D
authors.lastname: Bories
authors.forename: M C
authors.initials: MC
authors.lastname: Raynal
authors.forename: D H
authors.initials: DH
authors.lastname: Solomon
authors.forename: Z
authors.initials: Z
authors.lastname: Darzynkiewicz
authors.forename: Y E
authors.initials: YE
authors.lastname: Cayre
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003470:Culture Media; D004273:DNA, Neoplasm / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D005796:Genes; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D008969:Molecular Sequence Data; D053146:Myeloblastin; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
chemical_list: D003470:Culture Media; D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D053146:Myeloblastin