TWIST1 Plays a Pleiotropic Role in Determining the Anaplastic Thyroid Cancer Phenotype

被引:47
作者
Salerno, Paolo [2 ]
Garcia-Rostan, Ginesa [3 ,4 ]
Piccinin, Sara [5 ]
Bencivenga, Tammaro Claudio [2 ]
Di Maro, Gennaro [2 ]
Doglioni, Claudio [6 ]
Basolo, Fulvio [7 ]
Maestro, Roberta [5 ]
Fusco, Alfredo [2 ]
Santoro, Massimo [2 ]
Salvatore, Giuliana [1 ]
机构
[1] Univ Parthenope, Dipartimento Studi Ist & Sistemi Terr, I-80133 Naples, Italy
[2] Univ Naples Federico 2, CNR, Ist Endocrinol & Oncol Sperimentale, Dipartimento Biol & Patol Cellulare & Mol, I-80131 Naples, Italy
[3] Univ Porto, Inst Mol Pathol & Immunol, P-4200465 Oporto, Portugal
[4] Univ Valladolid, CSIC, Inst Biol & Genet Mol, Valladolid 47003, Spain
[5] Aviano Natl Canc Inst, Ist Ricovero & Cura Carattere Sci, Ctr Riferimento Oncol, I-33081 Aviano, Pordenone, Italy
[6] Univ Vita Salute San Raffaele, Ist Sci San Raffaele, I-20132 Milan, Italy
[7] Univ Pisa, Dept Surg, Div Pathol, I-56126 Pisa, Italy
关键词
TRANSCRIPTION FACTOR; TAXOL RESISTANCE; CARCINOMA-CELLS; PIK3CA GENE; MUTATION; MORPHOGENESIS; TRANSITION; EXPRESSION; PROTEINS; TUMORS;
D O I
10.1210/jc.2010-1182
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human tumors; it is characterized by chemoresistance, local invasion, and distant metastases. ATC is invariably fatal. Objective: The aim was to study the role of TWIST1, a basic helix-loop-helix transcription factor, in ATC. Design: Expression of TWIST1 was studied by immunohistochemistry and real-time PCR in normal thyroids and well-differentiated, poorly differentiated, and ATC. The function of TWIST1 was studied by RNA interference in ATC cells and by ectopic expression in well-differentiated thyroid carcinoma cells. Results: ATCs up-regulate TWIST1 with respect to normal thyroids as well as to poorly and well-differentiated thyroid carcinomas. Knockdown of TWIST1 by RNA interference in ATC cells reduced cell migration and invasion and increased sensitivity to apoptosis. The ectopic expression of TWIST1 in thyroid cells induced resistance to apoptosis and increased cell migration and invasion. Conclusions: TWIST1 plays a key role in determining malignant features of the anaplastic phenotype in vitro. (J Clin Endocrinol Metab 96: E772-E781, 2011)
引用
收藏
页码:E772 / E781
页数:10
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