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

Abstract

CONTEXT:

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.

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.

• Authors: Eleonora Borbone, Giancarlo Troncone, Angelo Ferraro, Zuzana Jasencakova, Lovorka Stojic, Francesco Esposito, Nadine Hornig, Alfredo Fusco, Valerio Orlando
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 96 Issue 4 Pg. 1029-38 (Apr 2011) ISSN: 1945-7197 [Electronic] United States
• PMID: 21289264 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• PAX8 Transcription Factor
• PAX8 protein, human
• Paired Box Transcription Factors
• Transcription Factors
• EZH2 protein, human
• Enhancer of Zeste Homolog 2 Protein
• Polycomb Repressive Complex 2

Topics

• Animals
• Cell Adhesion (genetics)
• Cell Line, Tumor
• Cell Proliferation
• Cell Transformation, Neoplastic (genetics)
• DNA-Binding Proteins (genetics, metabolism)
• Disease Progression
• Enhancer of Zeste Homolog 2 Protein
• Gene Expression Regulation, Neoplastic
• Gene Silencing (physiology)
• HeLa Cells
• Humans
• Mice
• Mice, Transgenic
• PAX8 Transcription Factor
• Paired Box Transcription Factors (genetics)
• Polycomb Repressive Complex 2
• Thyroid Carcinoma, Anaplastic
• Thyroid Neoplasms (genetics, pathology)
• Transcription Factors (genetics, metabolism)
• Up-Regulation (physiology)