دورية أكاديمية
أعرض في EDS

EZH2-shRNA-mediated upregulation of p21waf1/cip1 and its transcriptional enhancers with concomitant downmodulation of mutant p53 in pancreatic ductal adenocarcinoma.

التفاصيل البيبلوغرافية
العنوان: EZH2-shRNA-mediated upregulation of p21waf1/cip1 and its transcriptional enhancers with concomitant downmodulation of mutant p53 in pancreatic ductal adenocarcinoma.
المؤلفون: Batchu RB; Laboratory of Surgical Oncology & Developmental Therapeutics, Department of Surgery, Wayne State University, Detroit, MI; John D. Dingell VA Medical Center, Wayne State University, Detroit, MI. Electronic address: rbatchu@med.wayne.edu., Qazi AM, Gruzdyn OV, Semaan A, Seward SM, Chamala S, Dhulipala VB, Bouwman DL, Weaver DW, Gruber SA
المصدر: Surgery [Surgery] 2013 Oct; Vol. 154 (4), pp. 739-46; discussion 746-7.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Mosby Country of Publication: United States NLM ID: 0417347 Publication Model: Print Cited Medium: Internet ISSN: 1532-7361 (Electronic) Linking ISSN: 00396060 NLM ISO Abbreviation: Surgery Subsets: MEDLINE
أسماء مطبوعة: Publication: St. Louis, MO : Mosby
Original Publication: St. Louis.
مواضيع طبية MeSH: Adenocarcinoma/*genetics , Carcinoma, Pancreatic Ductal/*genetics , Cyclin-Dependent Kinase Inhibitor p21/*physiology , Genes, p53/*physiology , Pancreatic Neoplasms/*genetics , Polycomb Repressive Complex 2/*physiology , RNA, Small Interfering/*genetics, Adenocarcinoma/pathology ; Animals ; Apoptosis ; Carcinoma, Pancreatic Ductal/pathology ; Cell Line, Tumor ; Cyclin-Dependent Kinase Inhibitor p21/genetics ; Enhancer Elements, Genetic ; Enhancer of Zeste Homolog 2 Protein ; Humans ; Mice ; Pancreatic Neoplasms/pathology ; Polycomb Repressive Complex 2/genetics ; Up-Regulation
مستخلص: 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.
(Copyright © 2013 Mosby, Inc. All rights reserved.)
المشرفين على المادة: 0 (CDKN1A protein, human)
0 (Cyclin-Dependent Kinase Inhibitor p21)
0 (RNA, Small Interfering)
EC 2.1.1.43 (EZH2 protein, human)
EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein)
EC 2.1.1.43 (Polycomb Repressive Complex 2)
تواريخ الأحداث: Date Created: 20131001 Date Completed: 20131126 Latest Revision: 20161125
رمز التحديث: 20240628
DOI: 10.1016/j.surg.2013.06.041
PMID: 24074410
قاعدة البيانات: MEDLINE
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