Author of

• 15558

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  P3.07 - Poster Session/ Small Cell Lung Cancer (ID 223)

  • Event: WCLC 2015
  • Type: Poster
  • Track: Small Cell Lung Cancer
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)

  • 15560

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    P3.07-002 - RBM5 Expression Correlates with Decreased Proliferation and Increased Cisplatin-Mediated Apoptosis (ID 854)

    09:30 - 09:30  |  Author(s): S. Hunt
    • Abstract

    Background:
    Lung cancer is the leading cause of cancer-related deaths in Canada, for both men and women. Small cell lung cancer (SCLC) is one subtype of lung cancer, and accounts for 15-20% of lung cancer incidence. SCLC is an aggressive cancer and commonly develops resistance to drugs used to treat it, including platinum-based agents such as cisplatin. RBM5 is a lung cancer tumour suppressor gene that is generally downregulated in lung cancer, and deleted in some. RBM5 is an RNA-binding protein that has the ability to regulate the cell cycle and modulate apoptosis. We hypothesize that reintroduction of RBM5 into an RBM5-null SCLC cell will result in decreased cell proliferation and increased apoptotic-like cell death in the presence of cisplatin.
    
    Methods:
    A SCLC cell line with an endogenous RBM5 homozygous deletion, and two previously established stable GLC20 sublines (T2 and C4) that express different levels of RBM5, were used for in vitro mechanistic studies. Proliferation changes were monitored using an MTT assay and a cell counting assay. Cisplatin-induced cell death was monitored by assessing cell viability (by nigrosin staining), PARP cleavage (by Western blot), chromatin condensation and phosphatidylserine flip (by fluorescence microscopy).
    
    Results:
    Decreased proliferation was observed in the high (C4) but not the low RBM5 (T2) expressing subline, compared to either the parental GLC20 cells or the empty vector control subline. Increased cisplatin-mediated cell death, observed as PARP cleavage, was observed in both T2 and C4, compared to either the parental GLC20 cells or the empty vector control subline. Fluorescence microscopy results will be presented.
    
    Conclusion:
    These results suggest that the loss of RBM5 expression in SCLC cells leads to increased proliferation and survival of SCLC cells. We hope to demonstrate the potential role of RBM5 as a predictive marker for cisplatin sensitivity in SCLC.