Predictive Biomarkers and Personalized Medicine TP53GenomicStatusRegulates Sensitivity of GastricCancer Cells to the HistoneMethylation Inhibitor 3-Deazaneplanocin A (DZNep)

نویسندگان

  • Lai Ling Cheng
  • Yoko Itahana
  • Zheng Deng Lei
  • Na-Yu Chia
  • Yonghui Wu
  • Yingnan Yu
  • Shen Li Zhang
  • Aye Aye Thike
  • Anuradha Pandey
  • Steve Rozen
  • Pieter Mathijs Voorhoeve
  • Qiang Yu
  • Puay Hoon Tan
  • Boon Huat Bay
  • Koji Itahana
  • Patrick Tan
چکیده

Purpose: DZNep (3-deazaneplanocin A) depletes EZH2, a critical component of polycomb repressive complex 2 (PRC2), which is frequently deregulated in cancer. Despite exhibiting promising anticancer activity, the specific genetic determinants underlying DZNep responsiveness in cancer cells remain largely unknown. We sought to determine molecular factors influencing DZNep response in gastric cancer. Experimental Design: Phenotypic effects of DZNep were evaluated in a panel of gastric cancer cell lines. Sensitive lines were molecularly interrogated to identify potential predictors of DZNep responsiveness. The functional importance of candidate predictors was evaluated using short hairpin RNA (shRNA) and siRNA

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تاریخ انتشار 2012