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http://purl.uniprot.org/citations/24074410http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24074410http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

Enhancer of zeste homologue 2 (EZH2), a component of the chromatin modification protein complex, is upregulated in pancreatic ductal adenocarcinoma (PDAC), whereas loss of p53 and its downstream target, p21(waf1/cip1), is also observed frequently. We sought to investigate the role of the p53-p21(waf1/cip1) pathway in relation to EZH2-mediated inhibition of PDAC.

Methods

The PANC-1 cell line was utilized in chromatin immunoprecipitation, gene profiling, Western blot, cell invasion, cell proliferation, and tumor xenograft assays.

Results

Western blot analysis with antibodies that recognize both wild-type and mutant p53 did not show any alterations in band intensity; however, antibody that detects only mutant p53 showed a band of significantly lesser intensity with EZH2 knockdown. Western blot analysis further revealed a significant upregulation of p21(waf1/cip1). Gene expression profile analysis indicated significantly enhanced transcripts of transcriptional inducers of p21(waf1/cip1), with downregulation of mutant p53 transcript, corroborating the Western blot analysis. PANC-1 cells expressing EZH2-short hairpin RNA displayed markedly attenuated growth in SCID mice.

Conclusion

Downregulation of mutant p53 with concomitant enhanced expression of p21(waf1/cip1) and its transcriptional trans-activators may contribute toward EZH2-mediated suppression of PDAC."xsd:string
http://purl.uniprot.org/citations/24074410http://purl.org/dc/terms/identifier"doi:10.1016/j.surg.2013.06.041"xsd:string
http://purl.uniprot.org/citations/24074410http://purl.uniprot.org/core/author"Chamala S."xsd:string
http://purl.uniprot.org/citations/24074410http://purl.uniprot.org/core/author"Batchu R.B."xsd:string
http://purl.uniprot.org/citations/24074410http://purl.uniprot.org/core/author"Qazi A.M."xsd:string
http://purl.uniprot.org/citations/24074410http://purl.uniprot.org/core/author"Gruber S.A."xsd:string
http://purl.uniprot.org/citations/24074410http://purl.uniprot.org/core/author"Weaver D.W."xsd:string
http://purl.uniprot.org/citations/24074410http://purl.uniprot.org/core/author"Semaan A."xsd:string
http://purl.uniprot.org/citations/24074410http://purl.uniprot.org/core/author"Bouwman D.L."xsd:string
http://purl.uniprot.org/citations/24074410http://purl.uniprot.org/core/author"Gruzdyn O.V."xsd:string
http://purl.uniprot.org/citations/24074410http://purl.uniprot.org/core/author"Dhulipala V.B."xsd:string
http://purl.uniprot.org/citations/24074410http://purl.uniprot.org/core/author"Seward S.M."xsd:string
http://purl.uniprot.org/citations/24074410http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/24074410http://purl.uniprot.org/core/name"Surgery"xsd:string
http://purl.uniprot.org/citations/24074410http://purl.uniprot.org/core/pages"739-746"xsd:string
http://purl.uniprot.org/citations/24074410http://purl.uniprot.org/core/title"EZH2-shRNA-mediated upregulation of p21waf1/cip1 and its transcriptional enhancers with concomitant downmodulation of mutant p53 in pancreatic ductal adenocarcinoma."xsd:string
http://purl.uniprot.org/citations/24074410http://purl.uniprot.org/core/volume"154"xsd:string
http://purl.uniprot.org/citations/24074410http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24074410
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http://purl.uniprot.org/uniprot/#_A0A087WXZ1-mappedCitation-24074410http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24074410
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