title: ETS-1 induces increased expression of erythroid markers in the pluripotent erythroleukemic cell lines K562 and HEL.
abstract: Members of the ETS gene family are known to be expressed in hematopoietic tissues and cell lines, and there is increasing evidence that ETS proteins may play a role in normal hematopoietic cell development. We demonstrate that ETS-1 can contribute to the development of an erythroid phenotype in vitro. The pluripotent erythroleukemic K562 and HEL cell lines express messages for a number of ETS genes, but only c-ETS-1 levels are elevated in response to treatment with hemin or cytosine arabinofuranoside (Ara-C), agents which induce erythroid differentiation. Furthermore, ETS-1 antisense oligonucleotides inhibit hemoglobinization of cells treated with Ara-C or hemin, and K562 and HEL cells infected with retrovirus expressing the c-ETS-1 gene exhibit a significant increase in erythroid character (as indicated by benzidine staining for hemoglobin (Hb) and surface marker analysis), a dramatic increase in responsiveness to hemin or Ara-C, and a decreased rate of proliferation (20-40% of control rates). In contrast, infection with virus expressing ETS-2 or vector sequences only causes no detectable changes in the proliferation or erythroid character of either the HEL or K562 cell lines. These data indicate a role for ETS-1 in erythroid differentiation.
authors.affiliation: Division of Basic Sciences, National Cancer Institute, Frederick, MD 21702-1201, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Clausen
authors.forename: M
authors.initials: M
authors.lastname: Athanasiou
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: K J
authors.initials: KJ
authors.lastname: Dunn
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: J A
authors.initials: JA
authors.lastname: Lautenberger
authors.forename: G
authors.initials: G
authors.lastname: Mavrothalassitis
authors.forename: D G
authors.initials: DG
authors.lastname: Blair
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology; D004268:DNA-Binding Proteins; D004920:Erythropoiesis / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006427:Hemin / Q000494:pharmacology; D006454:Hemoglobins / Q000096:biosynthesis; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494041:ETS1 protein, human; C494069:ETS2 protein, human; D006454:Hemoglobins; D016376:Oligonucleotides, Antisense; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D003561:Cytarabine; D006427:Hemin