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M.N. Adams



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    P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P1.04-076 - CDCA3 Is a Novel Cell Cycle Regulator in Lung Cancer (ID 1630)

      09:30 - 09:30  |  Author(s): M.N. Adams

      • Abstract
      • Slides

      Background:
      Progression through the mammalian cell cycle relies upon coordination of a complex network of proteins. Following genomic insult, checkpoints during each stage of the cell cycle are engaged to halt cell cycle progression to allow faithful DNA repair. Failure to arrest cell cycle may lead to genomic instability and cancer development. However, the molecular basis for the loss of genome integrity during cancer development remains to be determined. Cell division cycle associated 3 (CDCA3) is a key regulator of the normal cell cycle. CDCA3 modulates this process by enabling cell entry into mitosis through degradation of the mitosis-inhibitory factor WEE1. CDCA3 itself is also degraded in G1 yet re-expressed in G2/M phase, to allow successful progression through the cell cycle. Here we describe for the first time a novel function for CDCA3 in maintaining effective cell cycle progression in lung cancer.

      Methods:
      To examine the role of CDCA3 in modulating the cell cycle of lung cancer cells, CDCA3 was depleted using an siRNA approach in A549, SKMES and H460 cell lines. CDCA3 depletion was assessed using Western blot analysis. Cell proliferation assays were performed on control and CDCA3 knockdown cells over a period of 96 h using the Promega CellTitre-Glo cell viability assay. Cell cycle progression was assessed on propidium iodide stained cells using a Beckman Coulter Gallios flow cytometer. To determine if CDCA3 expression is associated with lung cancer progression, a tissue microarray (TMA) with cores from 600 patients was stained with an anti-CDCA3 antibody. Correlation of CDCA3 staining with clinical data and patient prognosis is ongoing.

      Results:
      As a cell cycle related protein, we tested if CDCA3 is required for effective proliferation of a range of lung cancer cell lines. CDCA3 depletion reduced the proliferation of U2OS (osteosarcoma), A549, MOR (lung adenomcarcenoma) and SKMES cancer cells (squamous lung cancer). Interestingly, depletion of CDCA3 did not affect proliferation of H460 cells (large neuroendocrine lung cancer). We next tested the cell cycle progression and noted that knockdown of CDCA3 induced an increase of all cell lines in G1 arrest with the exception of H460 cells. To observe if CDCA3 expression is linked with disease progression, TMA staining of lung cancer biopsies was performed. Accordingly, elevated expression of CDCA3 was identified specifically in tumour cells. These data highlight the potential prognostic value of CDCA3 expression.

      Conclusion:
      Our data point to a potential role for CDCA3 in the progression of lung cancer. While the precise mechanism for CDCA3-dependent cell cycle regulation remains unknown, it is possible that elevated CDCA3 levels modulate tumour cell proliferation. Identifying the molecular basis may yield novel therapeutic avenues worth targeting during aberrant cell cycle in cancer.

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