Enhancer of zeste homolog 2 overexpression has a role in the development of anaplastic thyroid carcinomas

Eleonora Borbone, Giancarlo Troncone, Angelo Ferraro, Zuzana Jasencakova, Lovorka Stojic, Francesco Esposito, Nadine Hornig, Alfredo Fusco*, Valerio Orlando

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Context: Enhancer of zestehomolog2 (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. Objectives: 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.

Original languageEnglish (US)
Pages (from-to)1029-1038
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume96
Issue number4
DOIs
StatePublished - Apr 1 2011

ASJC Scopus subject areas

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

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