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.

Ccdc6 knock-in mice develop thyroid hyperplasia associated to an enhanced CREB1 activity / Leone, Vincenza; Langella, Concetta; Esposito, Francesco; Arra, Claudio; Palma, Giuseppe; Rea, Domenica; Paciello, Orlando; Merolla, Francesco; DE BIASE, Davide; Papparella, Serenella; Celetti, Angela; Fusco, Alfredo. - In: ONCOTARGET. - ISSN 1949-2553. - 6:17(2015), p. 15628-38. [10.18632/oncotarget.3858]

Ccdc6 knock-in mice develop thyroid hyperplasia associated to an enhanced CREB1 activity

LEONE, Vincenza;PACIELLO, ORLANDO;DE BIASE, DAVIDE;PAPPARELLA, SERENELLA;FUSCO, ALFREDO
2015

Abstract

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.
2015
Ccdc6 knock-in mice develop thyroid hyperplasia associated to an enhanced CREB1 activity / Leone, Vincenza; Langella, Concetta; Esposito, Francesco; Arra, Claudio; Palma, Giuseppe; Rea, Domenica; Paciello, Orlando; Merolla, Francesco; DE BIASE, Davide; Papparella, Serenella; Celetti, Angela; Fusco, Alfredo. - In: ONCOTARGET. - ISSN 1949-2553. - 6:17(2015), p. 15628-38. [10.18632/oncotarget.3858]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/612835
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