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
| Autor: | Hiroyuki Kawagoe, Gerard Grosveld, John R. M. Ellis, Mark D. Potter |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Transcriptional Activation
Cancer Research Cellular differentiation Biology Transfection Monocytes Mice Calcitriol Animals Humans RNA Messenger Transcription factor Regulation of gene expression Proto-Oncogene Proteins c-ets U937 cell Gene Expression Regulation Leukemic Reverse Transcriptase Polymerase Chain Reaction ETS transcription factor family Cell Differentiation U937 Cells Hematopoietic Stem Cells Molecular biology Up-Regulation DNA-Binding Proteins Repressor Proteins Haematopoiesis Cell Transformation Neoplastic Oncology Leukemia Myeloid Mutation NIH 3T3 Cells ras Proteins Monocytic leukemia Transcription Factors |
| Zdroj: | Cancer Research. 64:6091-6100 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-04-0839 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|