Tumor suppressor role of the CL2/DRO1/CCDC80 gene in thyroid carcinogenesis

Angelo Ferraro, Filippo Schepis, Vincenza Leone, Antonella Federico, Eleonora Borbone, Pierlorenzo Pallante, Maria Teresa Berlingieri, Gennaro Chiappetta, Mario Monaco, Dario Palmieri, Lorenzo Chiariotti, Massimo Santoro, Alfredo Fusco

Research output: Contribution to journalArticlepeer-review

Abstract

Context: Thyroid carcinoma is one of the mostcommonmalignancies of the endocrine system, and, despite the high frequency of oncogene activation in thyroid neoplastic lesions, the tumor suppressor genes involved in thyroid carcinogenesis remain unidentified.Ourprevious data implicated a link between the CL2/CCDC80 gene and thyroid cancer. Objective: The objective of the study was 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: Weevaluated 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 2 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 down-regulation in thyroid carcinoma samples. Restoration of CL2/CCDC80 expression in the 2 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 tumor suppressor gene in thyroid carcinogenesis.

Original languageEnglish
Pages (from-to)2834-2843
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume98
Issue number7
DOIs
Publication statusPublished - Jul 2013

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

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