Jul 17, 2013

EZH2 promotes E2F-driven SCLC tumorigenesis through modulation of apoptosis and cell-cycle regulation

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
Roland HubauxWan L Lam

Abstract

Although enhancer of zeste homolog 2 (EZH2) has been associated with both non-small cell and small-cell lung cancers (SCLCs), current observations suggest different mechanisms of EZH2 activation and overexpression in these lung cancer types. Globally, SCLC kills 200,000 people yearly. New clinical approaches for SCLC treatment are required to improve the poor survival rate. Given the therapeutic potential of EZH2 as a target, we sought to delineate the downstream consequences of EZH2 disruption to identify the cellular mechanisms by which EZH2 promotes tumorigenesis in SCLC. We generated cells with stable expression of short hairpin RNA targeting EZH2 and corresponding controls (pLKO.1) and determined the consequences of EZH2 knockdown on the cell cycle and apoptosis by means of propidium iodide staining and fluorescence-activated cell sorting, Western blot, quantitative reverse transcriptase-polymerase chain reaction as well as cell viability assessment using methylthiazol tetrazolium assays. We discovered that EZH2 inhibition (1) increased apoptotic activity by up-regulating the proapoptotic factors Puma and Bad, (2) decreased the fraction of cells in S or G2/M phases, and (3) elevated p21 protein levels, implicating EZH2 in ...Continue Reading

  • References15
  • Citations23

References

  • References15
  • Citations23

Citations

Mentioned in this Paper

Tumorigenicity
Apoptosis, Intrinsic Pathway
Oncoprotein p21
Western Blotting
Tetrazolium Salts
Fluorescence-Activated Cell Sorting
Propidium Iodide
BBC3 gene
Small Cell Carcinoma of Lung
Reverse Transcriptase Polymerase Chain Reaction

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