| First Author | Sangrar W | Year | 2005 |
| Journal | Cancer Res | Volume | 65 |
| Issue | 9 | Pages | 3518-22 |
| PubMed ID | 15867340 | Mgi Jnum | J:98281 |
| Mgi Id | MGI:3577795 | Doi | 10.1158/0008-5472.CAN-04-3468 |
| Citation | Sangrar W, et al. (2005) An identity crisis for fps/fes: oncogene or tumor suppressor?. Cancer Res 65(9):3518-22 |
| abstractText | Fps/Fes proteins were among the first members of the protein tyrosine kinase family to be characterized as dominant-acting oncoproteins. Addition of retroviral GAG sequences or other experimentally induced mutations activated the latent transforming potential of Fps/Fes. However, activating mutations in fps/fes had not been found in human tumors until recently, when mutational analysis of a panel of colorectal cancers identified four somatic mutations in sequences encoding the Fps/Fes kinase domain. Here, we report biochemical and theoretical structural analysis demonstrating that three of these mutations result in inactivation, not activation, of Fps/Fes, whereas the fourth mutation compromised in vivo activity. These results did not concur with a classic dominant-acting oncogenic role for fps/fes involving activating somatic mutations but instead raised the possibility that inactivating fps/fes mutations might promote tumor progression in vivo. Consistent with this, we observed that tumor onset in a mouse model of breast epithelial cancer occurred earlier in mice targeted with either null or kinase-inactivating fps/fes mutations. Furthermore, a fps/fes transgene restored normal tumor onset kinetics in targeted fps/fes null mice. These data suggest a novel and unexpected tumor suppressor role for Fps/Fes in epithelial cells. |
