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

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.

Cancer Lett ; 336(1): 53-60, 2013 Aug 09.

Article in English | MEDLINE | ID: mdl-23603558

ABSTRACT

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.

Subject(s)

Cyclin-Dependent Kinase Inhibitor p21/metabolism , Gene Expression Regulation, Neoplastic , Ovarian Neoplasms/pathology , Polycomb Repressive Complex 2/metabolism , RNA Interference , Tumor Suppressor Protein p53/metabolism , Animals , Apoptosis , Cell Line, Tumor , Cell Proliferation , Cyclin-Dependent Kinase Inhibitor p21/genetics , Enhancer of Zeste Homolog 2 Protein , Female , Humans , Mice , Mice, SCID , Mutation , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Transplantation , Oligonucleotide Array Sequence Analysis , Ovarian Neoplasms/genetics , Polycomb Repressive Complex 2/genetics , Tumor Suppressor Protein p53/genetics

ABSTRACT

Subject(s)

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