title: Tumor suppressor role of the CL2/DRO1/CCDC80 gene in thyroid carcinogenesis.
abstract: BACKGROUND
  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 tumor suppressor genes involved in thyroid carcinogenesis remain unidentified. Our previous 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.
  
  
  METHODS
  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 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.
authors.affiliation: Istituto per l'Endocrinologia e l'Oncologia Sperimentale G Salvatore, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Fondazione Pascale, 80131 Napoli, Italy. ferraro@eie.gr
authors.forename: Angelo
authors.initials: A
authors.lastname: Ferraro
authors.forename: Filippo
authors.initials: F
authors.lastname: Schepis
authors.forename: Vincenza
authors.initials: V
authors.lastname: Leone
authors.forename: Antonella
authors.initials: A
authors.lastname: Federico
authors.forename: Eleonora
authors.initials: E
authors.lastname: Borbone
authors.forename: Pierlorenzo
authors.initials: P
authors.lastname: Pallante
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Berlingieri
authors.forename: Gennaro
authors.initials: G
authors.lastname: Chiappetta
authors.forename: Mario
authors.initials: M
authors.lastname: Monaco
authors.forename: Dario
authors.initials: D
authors.lastname: Palmieri
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Chiariotti
authors.forename: Massimo
authors.initials: M
authors.lastname: Santoro
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
mesh_terms: D017209:Apoptosis; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins; D056726:Genetic Association Studies; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007558:Italy; D019656:Loss of Heterozygosity; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C492631:CCDC80 protein, human; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins