| First Author | Iotti G | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 10 | Pages | e48353 |
| PubMed ID | 23133585 | Mgi Jnum | J:192251 |
| Mgi Id | MGI:5464221 | Doi | 10.1371/journal.pone.0048353 |
| Citation | Iotti G, et al. (2012) Reduction of Prep1 levels affects differentiation of normal and malignant B cells and accelerates Myc driven lymphomagenesis. PLoS One 7(10):e48353 |
| abstractText | The Prep1 homeodomain transcription factor has recently been recognized as a tumor suppressor. Among other features, haploinsufficiency of Prep1 is able to strongly accelerate the B-lymphomagenesis in EmuMyc mice. Now we report that this occurs concomitantly with a change in the type of B-cell lymphomas generated by the Myc oncogene. Indeed, the tumors generated in the EmuMyc-Prep1(+/-) mice are much more immature, being mostly made up of Pro-B or Pre-B cells, while those in the EmuMyc-Prep1(+/+) mice are more differentiated being invariably IgM(+). Moreover, we show that Prep1 is in fact required for the differentiation of Pro-B and Pre-B cells into IgM(+) lymphocytes and/or their proliferation, thus showing also how a normal function of Prep1 affects EmuMyc lymphomagenesis. Finally, we show that the haploinsufficiency of Prep1 is accompanied with a major decrease of Myc-induced apoptosis and that the haploinsufficieny is sufficient for all these effects because the second allele of Prep1 is not lost even at late stages. Therefore, the tumor-suppressive activity of Prep1 is intertwined with both the interference with Myc-induced apoptosis as well as with natural developmental functions of the protein. |
