title: TEL2, an ETS factor expressed in human leukemia, regulates monocytic differentiation of U937 Cells and blocks the inhibitory effect of TEL1 on ras-induced cellular transformation.
abstract: TEL2 is a member of the ETS family of transcription factors, which is highly similar to TEL1/ETV6. It binds to DNA via the ETS domain and interacts with itself or TEL1 via the pointed domain. The expression of TEL2 in normal and leukemic hematopoietic cells suggests a role in hematopoietic development. In this article, we describe the role of TEL2 in hematopoietic differentiation and cellular transformation. Quantitative reverse transcription-PCR showed that the expression of TEL2 mRNA was down-regulated during monocytic differentiation of U937 and HL60 induced by 1,25-(OH)2 vitamin D3 and 12-O-tetradecanoylphorbol 13-acetate, respectively. Overexpression of TEL2 in U937 cells inhibited differentiation induced by vitamin D3. In contrast, overexpression of a TEL2 mutant lacking either the pointed domain or a functional ETS domain induced both differentiation of U937 cells and inhibited their growth in vitro and in vivo. In addition, these mutants blocked TEL2-mediated transcriptional repression of a synthetic promoter containing TEL2 binding sites. These data suggest that dominant-negative inhibition of TEL2 might cause differentiation. Quantitative reverse transcription-PCR demonstrated that TEL2 is expressed at higher level in some primary human leukemia samples than in normal bone marrow. Furthermore, overexpression of TEL2 in NIH3T3-UCLA cells blocked the inhibitory effect of TEL1 on Ras-induced cellular transformation. These results suggest that TEL2 may play an important role in hematopoiesis and oncogenesis.
authors.affiliation: Department of Genetics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawagoe
authors.forename: Mark
authors.initials: M
authors.lastname: Potter
authors.forename: John
authors.initials: J
authors.lastname: Ellis
authors.forename: Gerard C
authors.initials: GC
authors.lastname: Grosveld
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015973:Gene Expression Regulation, Leukemic; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000473:pathology / Q000502:physiology; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009000:Monocytes / Q000166:cytology* / Q000473:pathology; D009154:Mutation; D041681:NIH 3T3 Cells; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection; D020298:U937 Cells; D015854:Up-Regulation; D018631:ras Proteins / Q000235:genetics / Q000502:physiology*; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D002117:Calcitriol; D004268:DNA-Binding Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D018631:ras Proteins; D000097764:ETS Translocation Variant 6 Protein; C101003:ELF2 protein, human