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Article

The influence of the WWOX gene on the regulation of biological processes during endometrial carcinogenesis

  • Authors:
    • E. Płuciennik
    • M. Nowakowska
    • M. Gałdyszyńska
    • M. Popęda
    • A. K. Bednarek
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Carcinogenesis, Medical University of Lodz, 90-752 Lodz, Poland, Department of Comparative Endocrinology, Medical University of Lodz, 90-752 Lodz, Poland, Faculty of Biomedical Sciences and Postgraduate Education, Medical University of Lodz, 90-752 Lodz, Poland
  • Pages: 807-815
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    Published online on: January 27, 2016
       https://doi.org/10.3892/ijmm.2016.2469
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Abstract

The purpose of the present study was to investigate the role of WW domain containing oxidoreductase (WWOX) downregulation in biological cancer-related processes in normal (non-malignant) and cancer endometrial cell lines. We created an in vitro model using the normal endometrial cell line, THESC, and 2 endometrial cancer cell lines with varying degrees of differentiation, the Ishikawa (well-differentiated) and the MFE296 (moderately differentiated) cells, in which the WWOX tumor suppressor gene was silenced using Gipz lentiviral shRNA. In this model, we examined the changes in invasiveness via biological assays, such as zymography, migration through a basement membrane, the adhesion of cells to extracellular matrix proteins, anchorage-independent growth and colony formation assay. We also evaluated the correlation between the mRNA expression of the WWOX gene and genes involved in the processes of carcinogenesis, namely catenin beta-1 (CTNNB1) and zinc finger E-box binding homeobox 1 (ZEB1) (gene transcription), cadherin 1 (CDH1) and ezrin (EZR) (cell adhesion), vimentin (VIM) (structural proteins), as well as phosphatase and tensin homolog (PTEN) (tumor suppression) and secreted protein, acidic, cysteine-rich (osteonectin) (SPARC) (SPARC) (cell growth regulation) by RT-qPCR. Downregulation of the WWOX gene in the moderately differentiated MFE296 cell line caused decreased migratory capacity, and a reduction of matrix metalloproteinase-2 (MMP-2) activity. However, these cells grew in semisolid medium and exhibited higher expression of CDH1 and EZR (cell adhesion) and secreted protein, acidic, cysteine-rich (osteonectin) (SPARC) (cell growth regulation). Moreover, in the well-differentiated endometrial cancer (Ishikawa) cell line, WWOX gene silencing resulted in an increased ability of the cells to proliferate indefinitely. Additionally, WWOX regulated changes in adhesion potential in both the normal and cancer cell lines. Our results suggest that the WWOX tumor suppressor gene modulated the processes of cell motility, cell adhesion, gene expression and remodeling in endometrial cell lines.
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Copy and paste a formatted citation
Spandidos Publications style
Płuciennik E, Nowakowska M, Gałdyszyńska M, Popęda M and Bednarek AK: The influence of the WWOX gene on the regulation of biological processes during endometrial carcinogenesis. Int J Mol Med 37: 807-815, 2016.
APA
Płuciennik, E., Nowakowska, M., Gałdyszyńska, M., Popęda, M., & Bednarek, A.K. (2016). The influence of the WWOX gene on the regulation of biological processes during endometrial carcinogenesis. International Journal of Molecular Medicine, 37, 807-815. https://doi.org/10.3892/ijmm.2016.2469
MLA
Płuciennik, E., Nowakowska, M., Gałdyszyńska, M., Popęda, M., Bednarek, A. K."The influence of the WWOX gene on the regulation of biological processes during endometrial carcinogenesis". International Journal of Molecular Medicine 37.3 (2016): 807-815.
Chicago
Płuciennik, E., Nowakowska, M., Gałdyszyńska, M., Popęda, M., Bednarek, A. K."The influence of the WWOX gene on the regulation of biological processes during endometrial carcinogenesis". International Journal of Molecular Medicine 37, no. 3 (2016): 807-815. https://doi.org/10.3892/ijmm.2016.2469
Copy and paste a formatted citation
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Spandidos Publications style
Płuciennik E, Nowakowska M, Gałdyszyńska M, Popęda M and Bednarek AK: The influence of the WWOX gene on the regulation of biological processes during endometrial carcinogenesis. Int J Mol Med 37: 807-815, 2016.
APA
Płuciennik, E., Nowakowska, M., Gałdyszyńska, M., Popęda, M., & Bednarek, A.K. (2016). The influence of the WWOX gene on the regulation of biological processes during endometrial carcinogenesis. International Journal of Molecular Medicine, 37, 807-815. https://doi.org/10.3892/ijmm.2016.2469
MLA
Płuciennik, E., Nowakowska, M., Gałdyszyńska, M., Popęda, M., Bednarek, A. K."The influence of the WWOX gene on the regulation of biological processes during endometrial carcinogenesis". International Journal of Molecular Medicine 37.3 (2016): 807-815.
Chicago
Płuciennik, E., Nowakowska, M., Gałdyszyńska, M., Popęda, M., Bednarek, A. K."The influence of the WWOX gene on the regulation of biological processes during endometrial carcinogenesis". International Journal of Molecular Medicine 37, no. 3 (2016): 807-815. https://doi.org/10.3892/ijmm.2016.2469
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