| First Author | Kamata T | Year | 2010 |
| Journal | Cancer Res | Volume | 70 |
| Issue | 21 | Pages | 8475-86 |
| PubMed ID | 20978199 | Mgi Jnum | J:166215 |
| Mgi Id | MGI:4840126 | Doi | 10.1158/0008-5472.CAN-10-0603 |
| Citation | Kamata T, et al. (2010) BRAF inactivation drives aneuploidy by deregulating CRAF. Cancer Res 70(21):8475-86 |
| abstractText | Aspartate-594 is the third most common BRAF residue mutated in human cancer. Mutants of this residue are kinase inactive, and the mechanism(s) by which they contribute to cancer has remained perplexing. Using a conditional knock-in mouse model, we show that the (D594A)Braf mutant does not drive tumor development per se but is able to induce aneuploidy in murine splenocytes and mouse embryonic fibroblasts and contributes to immortalization through the propagation of aneuploid cells. (D594A)Braf lacks kinase activity but induces the related gene product Craf as well as the mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathway. Here, we show that the aneuploid phenotype is dependent on Craf. Treatment with the MEK inhibitor U0126 did not attenuate the emergence of aneuploidy but prevented the growth of aneuploid cells. These results provide a previously unidentified link between Craf and chromosomal stability, with important implications for our understanding of the development of cancers with driver mutations that hyperactivate Craf. |
