Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/30947
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
Source: 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
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