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Article

Functional redundancy of the Notch pathway in ovarian cancer cell lines

  • Authors:
    • Fernanda Silva
    • Ana Félix
    • Jacinta Serpa
  • View Affiliations / Copyright

    Affiliations: Chronic Diseases Research Center (CEDOC‑FCM‑UNL), NOVA Medical School, NOVA University of Lisbon, Lisbon 1169‑056, Portugal
  • Pages: 2686-2691
    |
    Published online on: August 5, 2016
       https://doi.org/10.3892/ol.2016.4959
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Abstract

Epithelial ovarian cancer is the most lethal gynecologic malignancy, despite advances in treatment. The most common histological type, high‑grade ovarian serous carcinoma (OSC) is usually diagnosed at an advanced stage, and although these types of tumors frequently respond to surgery and platinum‑based chemotherapy, they usually recur. Ovarian clear cell carcinoma (OCCC) is an unusual histological type, which is known to be intrinsically chemoresistant and is associated with poor prognosis in advanced stages. In recent years, genetic alterations and epigenetic modulation of signaling pathways have been reported in OSC and OCCC, including the overexpression of Notch pathway elements and histone deacetylases. Histone deacetylase inhibitors (HDACis), including vorinostat (suberoylanilide hydroxamic acid), alter the transcription of genes involved in cell growth, survival and apoptosis, and have become an attractive therapeutic approach. However, no previous work has addressed the effect of HDACis, and in particular vorinostat, on Notch signaling in ovarian cancer. Therefore, the present study aimed to investigate the modulation of the Notch pathway by vorinostat in ovarian cancer. Using immunofluorescence and quantitative polymerase chain reaction, the present results revealed that vorinostat activated the Notch pathway in OCCC and OSC cell lines, through different Notch ligands. In OCCC, the activation of the Notch pathway appeared to occur through Delta‑like (Dll) ligands 1, 2 and 3, whereas in OSC Dll1 and Jagged 1 and 2 ligands were involved. The activation of the Notch pathway by vorinostat, in OCCC and OSC cell lines, culminated in the increased expression of the same downstream transcription factors, hairy enhancer of split (Hes) 1 and 5, and Hes‑related proteins 1 and 2. In conclusion, vorinostat modulates the expression of several downstream targets of the Notch pathway and independent Notch receptors and ligands that are expressed in OSC and OCCC. This upregulation of the Notch pathway may explain why vorinostat therapy fails in ovarian carcinoma treatment, as shown in certain clinical trials.
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Copy and paste a formatted citation
Spandidos Publications style
Silva F, Félix A and Serpa J: Functional redundancy of the Notch pathway in ovarian cancer cell lines. Oncol Lett 12: 2686-2691, 2016.
APA
Silva, F., Félix, A., & Serpa, J. (2016). Functional redundancy of the Notch pathway in ovarian cancer cell lines. Oncology Letters, 12, 2686-2691. https://doi.org/10.3892/ol.2016.4959
MLA
Silva, F., Félix, A., Serpa, J."Functional redundancy of the Notch pathway in ovarian cancer cell lines". Oncology Letters 12.4 (2016): 2686-2691.
Chicago
Silva, F., Félix, A., Serpa, J."Functional redundancy of the Notch pathway in ovarian cancer cell lines". Oncology Letters 12, no. 4 (2016): 2686-2691. https://doi.org/10.3892/ol.2016.4959
Copy and paste a formatted citation
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Spandidos Publications style
Silva F, Félix A and Serpa J: Functional redundancy of the Notch pathway in ovarian cancer cell lines. Oncol Lett 12: 2686-2691, 2016.
APA
Silva, F., Félix, A., & Serpa, J. (2016). Functional redundancy of the Notch pathway in ovarian cancer cell lines. Oncology Letters, 12, 2686-2691. https://doi.org/10.3892/ol.2016.4959
MLA
Silva, F., Félix, A., Serpa, J."Functional redundancy of the Notch pathway in ovarian cancer cell lines". Oncology Letters 12.4 (2016): 2686-2691.
Chicago
Silva, F., Félix, A., Serpa, J."Functional redundancy of the Notch pathway in ovarian cancer cell lines". Oncology Letters 12, no. 4 (2016): 2686-2691. https://doi.org/10.3892/ol.2016.4959
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