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O. Vera
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-104 - Regulating the Response to Cisplatin in Lung Cancer Cells through the Transcription Factor TCF4: A New Potential Role for Wnt Signaling (ID 1647)
09:30 - 09:30 | Author(s): O. Vera
- Abstract
Background:
The standard treatment for non-small cell lung cancer (NSCLC) is Platinum-based chemotherapy, although the main clinical problem associated is the progression of the disease to a platinum-resistant state. This fact has limited its efficacy in these tumor types, which is one of the first causes of cancer deaths in developed countries. Thus, it is of great interest to identify predictive molecular biomarkers that could help in the patient treatment selection.
Methods:
In this study we used array-CGH to analyze the cytogenetic alterations that arise in NSCLC and ovarian cancer cells after cisplatin treatment, by using four paired sensitive(S) and resistant(R) cell lines: H23S/R, H460S/R, A2780S/R and OVCAR3S/R.
Results:
Our experimental approach revealed the presence of a common deletion of the gene TCF4 in a mosaic manner in at least 50% of the resistant cells in both tumor types, while a decrease in TCF4 expression was confirmed through qRT-PCR in the same cells. As TCF4 is a downstream transcription factor of Wnt signaling, we analyzed its potential role regulating the CDDP response in resistant cells through its action in the Wnt pathway. Combination of Top-Fop vectors and TCF4-cDNA overexpression plasmids showed firstly, that resistant cells responded easily to the activation of Wnt pathway, an effect in part mediated by the decrease in TCF4 expression; secondly the overexpression of TCF4 induced an increase in the Cisplatin sensitivity. These results indicate that TCF4 could be acting as a Wnt transcriptional repressor, maintaining the sensitivity to Cisplatin in A2780-S cells.
Conclusion:
Our translational approach in a total of 40 ovarian and lung primary tumors and in 14 normal tissues confirmed that TCF4 expression is frequently downregulated in these tumor types. Altogether we present a novel role for Wnt signaling pathway, regulating the response to CDDP, which could be a potential target for cancer treatment. Supported by ISCIII PI12/00386, ISCIII PI12/01463 and the Miguel Servet II program (CP08/00068) to I. Ibáñez de Cáceres
