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Leukemia-related transcription factor TEL accelerates differentiation of Friend erythroleukemia cells

Oncogene volume 22, pages 59–68 (2003)Cite this article

Abstract

TEL belongs to a member of the ETS family transcription factors that represses transcription of target genes such as FLI-1. Although TEL is essential for establishing hematopoiesis in neonatal bone marrow, its role in erythroid lineage is not understood. To investigate a role for TEL in erythroid differentiation, we introduced TEL into mouse erythroleukemia (MEL) cells. Overexpressing wild-type-TEL in MEL cells enhanced differentiation induced by hexamethylene bisacetamide or dimethylsulfoxide, as judged by the increased levels of erythroid-specific δ-aminolevulinate synthase and β-globin mRNAs. TEL bound to a corepressor mSin3A through the helix–loop–helix domain. A TEL mutant lacking this domain still bound to the ETS binding site, but lost its transrepressional effect. This mutant completely blocked erythroid differentiation in MEL cells. Moreover, it showed dominant-negative effects over TEL-mediated transcriptional repression and acceleration of erythroid differentiation. Endogenous TEL mRNA was found to increase during the first 3 days in differentiating MEL cells and drastically decrease thereafter. All these data suggest that TEL might play some role in erythroid cell differentiation.

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Acknowledgements

TEL10/pcDNA3 and pCMX-mSin3A were generous gifts from Dr TR Golub (Dana-Farber Cancer Institute, Boston, USA) and Dr RM Evans (The Salk Institute for Biological Studies, La Jolla, USA), respectively. ALAS-E probe, and pCXN2 and pCAGIPuro plasmids were kindly provided by Dr H Fujita (Hokkaido University, Sapporo, Japan) and Dr J Miyazaki (Osaka University, Osaka, Japan), respectively. We thank Dr Y Imai and Dr K Izutsu (Tokyo University) for fruitful discussions. We also thank Ms Y Furuta for special technical assistance. This work was financially supported in part by Grants-in-Aid for Cancer Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan, from the Ministry of Health, Labour and Welfare, Japan, and from the Japanese Society for the Promotion of Science. It was also supported by Research Grant of the Princess Takamatsu Cancer Research Fund, Seki Minato Memorial Award, Novartis Foundation (Japan) for the Promotion of Science, Japanese Clinical Oncology Fund, and Foundation for Promotion of Cancer Research in Japan.

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Authors and Affiliations

  1. Department of Hematology, Dokkyo University School of Medicine, 321-0293, Tochigi, Japan

    Kazuo Waga, Yuichi Nakamura, Kazuhiro Maki, Honoka Arai, Ko Sasaki & Kinuko Mitani

  2. Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, 113-8655, Japan

    Tetsuya Yamagata, Mineo Kurokawa & Hisamaru Hirai

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  1. Kazuo Waga
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Waga, K., Nakamura, Y., Maki, K. et al. Leukemia-related transcription factor TEL accelerates differentiation of Friend erythroleukemia cells. Oncogene 22, 59–68 (2003). https://doi.org/10.1038/sj.onc.1206072

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