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

Vincenza Leone, Concetta Langella, Francesco Esposito, Claudio Arra, Giuseppe Palma, Domenica Rea, Orlando Paciello, Francesco Merolla, Davide De Biase, Serenella Papparella, Angela Celetti, Alfredo Fusco

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)15628-15638
Number of pages11
JournalOncotarget
Volume6
Issue number17
Publication statusPublished - 2015

Fingerprint

Hyperplasia
Thyroid Gland
Oncogenes
Exons
Genes
Alleles
Proteins
Papillary Thyroid cancer

Keywords

  • Ccdc6
  • CREB1
  • Knock-in mice
  • Thyroid

ASJC Scopus subject areas

  • Oncology

Cite this

Leone, V., Langella, C., Esposito, F., Arra, C., Palma, G., Rea, D., ... Fusco, A. (2015). Ccdc6 knock-in mice develop thyroid hyperplasia associated to an enhanced CREB1 activity. Oncotarget, 6(17), 15628-15638.

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; Biase, Davide De; Papparella, Serenella; Celetti, Angela; Fusco, Alfredo.

In: Oncotarget, Vol. 6, No. 17, 2015, p. 15628-15638.

Research output: Contribution to journalArticle

Leone, V, Langella, C, Esposito, F, Arra, C, Palma, G, Rea, D, Paciello, O, Merolla, F, Biase, DD, Papparella, S, Celetti, A & Fusco, A 2015, 'Ccdc6 knock-in mice develop thyroid hyperplasia associated to an enhanced CREB1 activity', Oncotarget, vol. 6, no. 17, pp. 15628-15638.
Leone, Vincenza ; Langella, Concetta ; Esposito, Francesco ; Arra, Claudio ; Palma, Giuseppe ; Rea, Domenica ; Paciello, Orlando ; Merolla, Francesco ; Biase, Davide De ; Papparella, Serenella ; Celetti, Angela ; Fusco, Alfredo. / Ccdc6 knock-in mice develop thyroid hyperplasia associated to an enhanced CREB1 activity. In: Oncotarget. 2015 ; Vol. 6, No. 17. pp. 15628-15638.
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