title: EZH2 blockade by RNA interference inhibits growth of ovarian cancer by facilitating re-expression of p21(waf1/cip1) and by inhibiting mutant p53.
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.
authors.affiliation: Laboratory of Surgical Oncology & Developmental Therapeutics, Department of Surgery, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Shelly
authors.initials: S
authors.lastname: Seward
authors.forename: Assaad
authors.initials: A
authors.lastname: Semaan
authors.forename: Aamer M
authors.initials: AM
authors.lastname: Qazi
authors.forename: Oksana V
authors.initials: OV
authors.lastname: Gruzdyn
authors.forename: Sreedhar
authors.initials: S
authors.lastname: Chamala
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Bryant
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.forename: David
authors.initials: D
authors.lastname: Cameron
authors.forename: Seema
authors.initials: S
authors.lastname: Sethi
authors.forename: Rouba
authors.initials: R
authors.lastname: Ali-Fehmi
authors.forename: Robert
authors.initials: R
authors.lastname: Morris
authors.forename: David L
authors.initials: DL
authors.lastname: Bouwman
authors.forename: Adnan R
authors.initials: AR
authors.lastname: Munkarah
authors.forename: Donald W
authors.initials: DW
authors.lastname: Weaver
authors.forename: Scott A
authors.initials: SA
authors.lastname: Gruber
authors.forename: Ramesh B
authors.initials: RB
authors.lastname: Batchu
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009154:Mutation; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2