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
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container_end_page 60
container_issue 1
container_start_page 53
container_title Cancer letters
container_volume 336
creator 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
description 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.
doi_str_mv 10.1016/j.canlet.2013.04.012
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subjects 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
title EZH2 blockade by RNA interference inhibits growth of ovarian cancer by facilitating re-expression of p21(waf1/cip1) and by inhibiting mutant p53
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