Please use this identifier to cite or link to this item:
|Title:||P53 GENOMIC STATUS REGULATES SENSITIVITY OF GASTRIC CANCER CELLS TO THE HISTONE METHYLATION INHIBITOR 3-DEAZANEPLANOCIN A (DZNEP)||Authors:||CHENG LAI LING||Keywords:||DZNep, Gastric Cancer, Histone Methylation, Epigenetics, p53, USP10||Issue Date:||9-Sep-2011||Citation:||CHENG LAI LING (2011-09-09). P53 GENOMIC STATUS REGULATES SENSITIVITY OF GASTRIC CANCER CELLS TO THE HISTONE METHYLATION INHIBITOR 3-DEAZANEPLANOCIN A (DZNEP). ScholarBank@NUS Repository.||Abstract:||The polycomb complex member EZH2 is highly expressed in gastric cancer (GC) where it acts to suppress GC-related tumor suppressor genes. Here, we investigated the cellular and molecular effects of inhibiting EZH2 in GC cell lines, using a recently described small molecule (DZNep) that induces EZH2 depletion. We found that DZNep significantly suppressed the growth of only a subset of GC cell lines, and that DZNep-sensitive lines exhibited a significant tendency to carry wild-type p53 genes (P<0.001). Using functional assays, we demonstrate the existence of a novel mechanism of p53-dependent DZNep cellular sensitivity, involving p53 stabilization via USP10 upregulation. Finally, we show that in primary GCs, EZH2 expression is negatively correlated with p53 pathway activity, highlighting a potentially important role for EZH2 in repressing p53 activity. We propose that future clinical trials evaluating EZH2-targeting agents such as DZNep in GC should preselect patients by their p53 genomic status.||URI:||http://scholarbank.nus.edu.sg/handle/10635/30947|
|Appears in Collections:||Ph.D Theses (Open)|
Show full item record
Files in This Item:
|CHENGlailing_HT061917A.pdf||19.86 MB||Adobe PDF|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.