Tumour Suppressor Role of the CL2/DRO1/CCDC80 Gene in Thyroid Carcinogenesis.

Context.Thyroid carcinoma is one of the most common malignancies of the endocrine system and, despite the high frequency of oncogene activation in thyroid neoplastic lesions, the tumour suppressor genes involved in thyroid carcinogenesis remain unidentified. Our previous data implicated a link between the CL2/CCDC80 gene and thyroid cancer.Objective.To examine the expression of the CL2/CCDC80 gene in human thyroid carcinomas in the attempt to determine whether it plays a role in thyroid carcinogenesis.Design.We evaluated the expression of CL2/CCDC80 in a large number of thyroid neoplastic tissue samples differing in degree of malignancy. We also investigated the effects of its restoration in two human thyroid carcinoma cell lines characterized by very low levels of CL2/CCDC80 expression.Results.CL2/CCDC80 expression was much lower in almost all the thyroid carcinomas analyzed than in normal thyroid tissues, and was lowest in follicular variants of papillary carcinomas. Loss of heterozygosity partially accounted for CL2/CCDC80 downregulation in thyroid carcinoma samples. Restoration of CL2/CCDC80 expression in the two human thyroid anaplastic carcinoma cell lines resulted in a higher susceptibility to apoptosis and suppression of the malignant phenotype. CL2/CCDC80 expression positively regulated the expression of E-cadherin thereby halting cancer progression.Conclusions.These results indicate that CL2/CCDC80 is a putative tumour suppressor gene in thyroid carcinogenesis.