| First Author | Mikkers H | Year | 2002 |
| Journal | Oncogene | Volume | 21 |
| Issue | 43 | Pages | 6559-66 |
| PubMed ID | 12242653 | Mgi Jnum | J:79057 |
| Mgi Id | MGI:2387055 | Doi | 10.1038/sj.onc.1205930 |
| Citation | Mikkers H, et al. (2002) Proviral activation of the tumor suppressor E2a contributes to T cell lymphomagenesis in EmicroMyc transgenic mice. Oncogene 21(43):6559-66 |
| abstractText | The basic helix-loop-helix factor E2A plays an important role in the development of B and T lymphocytes. In addition, E2a has been implicated as a gene with tumor suppressor activity, since mice deficient for E2a succumb to T cell lymphomas. We have performed retroviral tagging in EmicroMyc transgenic mice to identify genes that contribute to lymphomagenesis. The EmicroMyc transgenic mouse is a well-established model of a common translocation in human B cell lymphomas. Analyses of the proviral insertion sites in the MuLV-induced lymphomas revealed that a number of T cell lymphomas carried proviral insertions in the promoter region of E2a. These proviral insertions yield hybrid viral-E2a mRNAs resulting in a marked rise in E2A protein levels. The proviral insertions in E2a were predominantly of clonal origin indicating that E2a insertions are early events in these T cell lymphomas. The primary oncogenic effect of E2A is likely to be associated with enhancement of transcription of the c-Myc transgene via binding to the regulatory immunoglobulin enhancers. The results herein thus provide the first evidence that in a specific setting E2A overexpression can contribute to T-lymphomagenesis. This implies that E2a contains oncogenic features in addition to the previously described tumor suppressive properties. |
