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  P3.02 - Poster Session 3 - Novel Cancer Genes and Pathways (ID 149)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

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    P3.02-021 - Interdependent role of MUC16/TSPYL5 in lung cancer cell proliferation (ID 3434)

    09:30 - 09:30  |  Author(s): M. Jain
    • Abstract

    Background
    Lung cancer is the leading cause of cancer-related mortality in the world. These patients usually present at an advanced stage where treatment is mostly palliative. Hence, there is an urgent need to investigate the various pre-neoplastic pathways to identify suitable therapeutic targets to decrease lung cancer mortality. The expression patterns of mucins are drastically altered during lung cancer development, and these alterations facilitate lung cancer cell proliferation and metastasis. MUC16 mucin and Testis specific Y-like protein TSPYL5 are two proteins that are overexpressed in lung cancer and appear to promote growth of lung cancer cells. In addition overexpression of TSPYL5 facilitates chemoresistance and regulates aromatase (CYP19A1) enzyme expression. This study was conducted to assess the interplay between these two markers and evaluate their effect of cisplatin induced cytotoxicity in lung cancer cells.

    Methods
    Expression of MUC16 in normal lung as well as lung carcinoma tissues in a commercially available tissue array was assessed by immunohistochemical (IHC) analysis using MUC16 antibody (DAKO Company-M11 clone). MUC16 levels were semi-quantified using a composite score based on the intensity and extent of staining. Endogenously expressed MUC16 and TSPYL5 were stably knocked down using a MUC16 shRNA construct (pSUPER-Retro-MUC16-sh) and TSPYL5 ShRNA construct in H292 and H827 lung cancer cells by stable transfection method for investigating the oncogenic functions. Lung cancer cells were treated with cisplatin to examine the role of MUC16 and TSPYL5 on chemoresistance and survival in lung cancer cells.

    Results
    MUC16 is highly expressed in lung carcinoma and is not expressed in non-neoplastic lung tissues. MUC16 composite IHC scores increased progressively from stage I to stage III NSCLC. Knockdown of MUC16 led to decreased proliferation (due to G1 accumulation), invasion and motility in H292 lung cancer cells. TSPYL5 was significantly downregulated in MUC16 knockdown cells. TSYPL5 knockdown in H292 lung cancer cells resulted in decreased expression of MUC16 as well as aromatase. The knockdown studies suggested that silencing of MUC16 and TSPYL5 affected each other. These results indicate that there may be a feedback regulation between these two molecules during lung cancer cell proliferation. Furthermore, cisplatin treatment of these cells significantly abrogated MUC16 and TSPYL5 expression.

    Conclusion
    MUC16 is overexpressed in non small cell lung cancer. MUC16 plays an important role in lung cancer proliferation, through rapid G1/S transition in the cell cycle. MUC16 and TSPYL5 regulate each other during lung cancer cell proliferation, possibly through the aromatase pathway. One of the possible mechanisms through which cisplatin may decrease lung cancer proliferation is by downregulation of MUC16 and TSPYL5.