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

被引:33
作者
Ferraro, Angelo [1 ,3 ]
Schepis, Filippo [4 ]
Leone, Vincenza [1 ,3 ]
Federico, Antonella [1 ,3 ]
Borbone, Eleonora [1 ,3 ]
Pallante, Pierlorenzo [1 ,3 ]
Berlingieri, Maria Teresa [1 ,3 ]
Chiappetta, Gennaro [2 ]
Monaco, Mario [2 ]
Palmieri, Dario [1 ]
Chiariotti, Lorenzo [1 ,3 ]
Santoro, Massimo [1 ,3 ]
Fusco, Alfredo [1 ,3 ]
机构
[1] Univ Naples Federico II, Ist Endocrinol & Oncol Sperimentale G Salvatore, Ist Endocrinol & Oncol Sperimentale, Consiglio Nazl Ric,Dipartimento Med Mol & Biotecn, I-80131 Naples, Italy
[2] Fdn Pascale, Ist Nazl Tumori, I-80131 Naples, Italy
[3] Ctr Ingn Genet Biotecnol Avanzate, Naples Oncoge Ctr, I-80145 Naples, Italy
[4] Univ Catanzaro Magna Graecia, Dipartimento Med Sperimentale, Fac Med & Chirurg Catanzaro, I-88100 Catanzaro, Italy
关键词
PHOSPHATASE-ETA SUPPRESSES; POINT MUTATIONS; HIGH PREVALENCE; BRAF MUTATIONS; P53; MUTATIONS; CARCINOMAS; EXPRESSION; CANCER; REARRANGEMENT; ACTIVATION;
D O I
10.1210/jc.2012-2926
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 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. 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 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.
引用
收藏
页码:2834 / 2843
页数:10
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