The cl2/dro1/ccdc80 null mice develop thyroid and ovarian neoplasias

Cancer Lett. 2015 Feb 28;357(2):535-41. doi: 10.1016/j.canlet.2014.12.010. Epub 2014 Dec 9.


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.

Keywords: Carcinoma; Knock-out mice; Ovary; Thyroid; cl2/dro1/ccdc80.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Breast Neoplasms / genetics
  • Carcinoma, Papillary / genetics
  • Cell Proliferation
  • Cells, Cultured
  • Colorectal Neoplasms / genetics
  • Embryo, Mammalian / cytology
  • Extracellular Matrix Proteins
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins / genetics*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Male
  • Mice, Knockout
  • Mice, Transgenic
  • Oncogene Proteins, Fusion / genetics
  • Ovarian Neoplasms / genetics*
  • Protein-Tyrosine Kinases / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thyroid Neoplasms / genetics*
  • Tumor Suppressor Proteins / genetics


  • CCDC80 protein, human
  • Ccdc80 protein, mouse
  • Extracellular Matrix Proteins
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Oncogene Proteins, Fusion
  • Tumor Suppressor Proteins
  • Protein-Tyrosine Kinases
  • Ret-Ptc1 oncoprotein, mouse