The Ets Factor Tel2 is a Hematopoietic Oncoprotein.
From: Department of Genetics and Tumor Cell Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.
Blood
- Publish Date: Feb 2006
- ISSN: 0006-4971
- Volume: 107
- Issue: 3
- Pages: 1124-32
- Medium: Print
- Language: English
- Citation (JAMA): Carella Cintia, Potter Mark, Bonten Jacqueline, et al. The Ets Factor Tel2 is a Hematopoietic Oncoprotein.. Blood Feb 2006;107:1124-32
Abstract
TEL2/ETV7 is highly homologous to the ETS transcription factor TEL/ETV6, a frequent target of chromosome translocation in human leukemia. Although both proteins are transcriptional inhibitors binding similar DNA recognition sequences, they have opposite biologic effects: TEL inhibits proliferation while TEL2 promotes it. In addition, forced expression of TEL2 but not TEL blocks vitamin D3-induced differentiation of U937 and HL60 myeloid cells. TEL2 is expressed in the hematopoietic system, and its expression is up-regulated in bone marrow samples of some patients with leukemia, suggesting a role in oncogenesis. Recently we also showed that TEL2 cooperates with Myc in B lymphomagenesis in mice. Here we show that forced expression of TEL2 alone in mouse bone marrow causes a myeloproliferative disease with a long latency period but with high penetrance. This suggested that secondary mutations are necessary for disease development. Treating mice receiving transplants with TEL2-expressing bone marrow with the chemical carcinogen N-ethyl-N-nitrosourea (ENU) resulted in significantly accelerated disease onset. Although the mice developed a GFP-positive myeloid disease with 30% of the mice showing elevated white blood counts, they all died of T-cell lymphoma, which was GFP negative. Together our data identify TEL2 as a bona fide oncogene, but leukemic transformation is dependent on secondary mutations.
Mesh Headings (Keywords): Alkylating Agents, Animals, Bone Marrow, Bone Marrow Transplantation, Carcinogens, Cell Transformation, Neoplastic, Ethylnitrosourea, Female, Gene Expression, HL-60 Cells, Hematopoiesis, Humans, Lymphoma, T-Cell, Male, Mice, Proto-Oncogene Proteins c-ets, Repressor Proteins, Transcription Factors, Translocation, Genetic, U937 Cells
Check for Full Text / PubMed Unique Identifier (PMID): 16234363
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