期刊
CANCER LETTERS
卷 357, 期 2, 页码 535-541出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2014.12.010
关键词
Knock-out mice; cl2/dro1/ccdc80; Thyroid; Ovary; Carcinoma
类别
资金
- AIRC [IG 11477]
- Progetto di Interesse strategico Invecchiamento (PNR-CNR Aging Program)
- POR Campania FSE Progetto CREMe
- Progetto Nuove strategie nanotecnologiche per la messa a punto di farmaci e presidi diagnostici diretti verso cellule cancerose circolanti [PON01-02782]
- Epigenomics CNR Flagship Project EPIGEN
- Nanomax CNR Flagship Project DESIRED
- Ministero dell'Istruzione, dell'Universita e della Ricerca MIUR
- Italian Ministry of Economy and Finance
We have previously reported that the expression of the CL2/CCDC80 gene is downregulated in human papillary thyroid carcinomas, particularly in follicular variants. We have also reported that the restoration of CL2/CCDC80 expression reverted the malignant phenotype of thyroid carcinoma cell lines and that CL2/CCDC80 positively regulated E-cadherin expression, an ability that likely accounts for the role of the CL2/CCDC80 gene in thyroid cancer progression. In order to validate the tumour suppressor role of the CL2/CCDC80 gene in thyroid carcinogenesis we generated cl2/ccdc80 knock-out mice. We found that embryonic fibroblasts from cl2/ccdc80-/- mice showed higher proliferation rate and lower susceptibility to apoptosis. Furthermore, cl2/ccdc80-/- mice developed thyroid adenomas and ovarian carcinomas. Finally, ret/PTC1 transgenic mice crossed with the cl2/ccdc80 knock-out mice developed more aggressive thyroid carcinomas compared with those observed in the single ret/PTC1 transgenic mice. Together, these results indicate CL2/CCDC80 as a putative tumour suppressor gene in human thyroid carcinogenesis. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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