ETS-1 induces increased expression of erythroid markers in the pluripotent erythroleukemic cell lines K562 and HEL.
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.
Clausen
P A
PA
Division of Basic Sciences, National Cancer Institute, Frederick, MD 21702-1201, USA.
Athanasiou
M
M
Chen
Z
Z
Dunn
K J
KJ
Zhang
Q
Q
Lautenberger
J A
JA
Mavrothalassitis
G
G
Blair
D G
DG
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
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