| First Author | Leone V | Year | 2015 |
| Journal | Oncotarget | Volume | 6 |
| Issue | 17 | Pages | 15628-38 |
| PubMed ID | 25970781 | Mgi Jnum | J:301625 |
| Mgi Id | MGI:6506937 | Doi | 10.18632/oncotarget.3858 |
| Citation | Leone V, et al. (2015) Ccdc6 knock-in mice develop thyroid hyperplasia associated to an enhanced CREB1 activity. Oncotarget 6(17):15628-38 |
| abstractText | CCDC6 was originally identified upon rearrangement with RET in human thyroid papillary carcinomas generating the RET/PTC1 oncogene. We have previously reported that CCDC6 interacts with CREB1 and represses its transcriptional activity. Since the function of at least one allele of CCDC6 is lost following RET/PTC1 rearrangements, we aimed at the generation of mice, carrying a CCDC6 mutant gene. Previous studies suggested that the coiled-coil domain of CCDC6, mainly encoded by human exon 2, is required for the protein function. Therefore, we engineered a murine Ccdc6 construct, carrying a deletion of the exon 2, that was able to exert only a mild repression on CREB1 transcriptional activity, with respect to the wild type Ccdc6. Subsequently, we generated Ccdc6-ex2 knock-in mice. These mice developed thyroid hyperplasia associated with an enhanced CREB1 activity and an increased expression of the CREB-1 regulated genes. These results strongly support a CCDC6 promoting role, ascribed to its functional impairment, in the development of thyroid papillary carcinomas harboring the RET/PTC1 oncogene. |
