title: Enhancer of zeste homolog 2 overexpression has a role in the development of anaplastic thyroid carcinomas.
abstract: BACKGROUND
  Enhancer of zeste homolog 2 (EZH2) is a histone lysine methyltransferase belonging to the polycomb group protein family. Overexpression of EZH2 has been found in several human malignancies including hematological and solid tumors.
  
  
  OBJECTIVE
  In this study we investigated the expression levels of EZH2 and its polycomb group protein partners in thyroid carcinoma tissues with different degrees of malignancy to identify potential new therapeutic targets for anaplastic thyroid carcinoma (ATC).
  
  
  RESULTS
  We show that high EZH2 expression levels are characteristic of undifferentiated ATC, whereas no significant changes were observed in well-differentiated papillary and follicular thyroid carcinomas as compared with normal thyroid. Knockdown of EZH2 in ATC cell lines results in cell growth inhibition, loss of anchorage-independent growth, migration, and invasion properties. Moreover, we demonstrate that EZH2 directly controls differentiation of ATC cells by silencing the thyroid specific transcription factor paired-box gene 8 (PAX8).
  
  
  CONCLUSIONS
  EZH2 is specifically overexpressed in ATC, and it directly contributes to transcriptional silencing of PAX8 gene and ATC differentiation.
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale-Consiglio Nazionale delle Ricerche, Università di Napoli Federico II,80131 Naples, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Borbone
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Troncone
authors.forename: Angelo
authors.initials: A
authors.lastname: Ferraro
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Jasencakova
authors.forename: Lovorka
authors.initials: L
authors.lastname: Stojic
authors.forename: Francesco
authors.initials: F
authors.lastname: Esposito
authors.forename: Nadine
authors.initials: N
authors.lastname: Hornig
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
authors.forename: Valerio
authors.initials: V
authors.lastname: Orlando
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D000071221:Enhancer of Zeste Homolog 2 Protein; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D063151:Polycomb Repressive Complex 2; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2