EZH2 blockade by RNA interference inhibits growth of ovarian cancer by facilitating re-expression of p21(waf1/cip1) and by inhibiting mutant p53

The enhancer of zeste homolog 2 (EZH2) methyltransferase is a transcriptional repressor. EZH2 is abnormally elevated in epithelial ovarian cancer (EOC). We demonstrated that EZH2 knockdown inhibited cell growth, activated apoptosis, and enhanced chemosensitivity. Further, silencing of EZH2 resulted...

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Veröffentlicht in:	Cancer letters 2013-08, Vol.336 (1), p.53-60
Hauptverfasser:	Seward, Shelly, Semaan, Assaad, Qazi, Aamer M, Gruzdyn, Oksana V, Chamala, Sreedhar, Bryant, Christopher C, Kumar, Sanjeev, Cameron, David, Sethi, Seema, Ali-Fehmi, Rouba, Morris, Robert, Bouwman, David L, Munkarah, Adnan R, Weaver, Donald W, Gruber, Scott A, Batchu, Ramesh B
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Apoptosis Cell Line, Tumor Cell Proliferation Cyclin-Dependent Kinase Inhibitor p21 - genetics Cyclin-Dependent Kinase Inhibitor p21 - metabolism Enhancer of Zeste Homolog 2 Protein Female Gene Expression Regulation, Neoplastic Humans Mice Mice, SCID Mutation Neoplasm Invasiveness Neoplasm Metastasis Neoplasm Transplantation Oligonucleotide Array Sequence Analysis Ovarian Neoplasms - genetics Ovarian Neoplasms - pathology Polycomb Repressive Complex 2 - genetics Polycomb Repressive Complex 2 - metabolism RNA Interference Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism
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Zusammenfassung:	The enhancer of zeste homolog 2 (EZH2) methyltransferase is a transcriptional repressor. EZH2 is abnormally elevated in epithelial ovarian cancer (EOC). We demonstrated that EZH2 knockdown inhibited cell growth, activated apoptosis, and enhanced chemosensitivity. Further, silencing of EZH2 resulted in re-expression of p21(waf1/cip1) and down-regulation of mutant p53. Finally, EZH2 knockdown contributed to attenuated EOC growth in SCID mice.
ISSN:	1872-7980
DOI:	10.1016/j.canlet.2013.04.012