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Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

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Article

Fibulin-5 localisation in human endometrial cancer shifts from epithelial to stromal with increasing tumour grade, and silencing promotes endometrial epithelial cancer cell proliferation

  • Authors:
    • Amy Louise Winship
    • Kate Rainczuk
    • Amanda Ton
    • Eva Dimitriadis
  • View Affiliations / Copyright

    Affiliations: Centre for Reproductive Health, The Hudson Institute of Medical Research, Melbourne, Victoria 3168, Australia
  • Pages: 651-657
    |
    Published online on: June 1, 2016
       https://doi.org/10.3892/ol.2016.4650
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Abstract

Endometrial cancer is the most common invasive gynaecological malignancy. While endocrine, genetic and inflammatory factors are thought to contribute to its pathogenesis, its precise etiology and molecular regulators remain poorly understood. Fibulin‑5 is an extracellular matrix (ECM) protein that inhibits cell growth and invasion in several cancer cell types and is downregulated in a number of types of human cancer. However, it is unknown whether fibulin‑5 plays a role in endometrial tumourigenesis. In the current report, the expression and localisation of fibulin‑5 in type I endometrioid human endometrial cancers of grades (G) 1‑3 was investigated using reverse transcription‑quantitative polymerase chain reaction and immunohistochemistry. Fibulin‑5 mRNA was found to be significantly reduced in whole tumour tissues from women across G1‑3 compared with benign endometrium (P<0.0001). Consistently, fibulin‑5 protein was also reduced in the tumour epithelial compartment across increasing tumour grades. By contrast, increased protein localisation to the tumour stroma was observed with increasing grade. Knockdown by small interfering RNA in Ishikawa endometrial epithelial cancer cells expressing fibulin‑5 stimulated cell adhesion and proliferation in vitro. Fibulin‑5 mRNA expression in Ishikawa cells was induced by transforming growth factor‑β and fibulin‑5 in turn activated extracellular signal‑regulated kinases (ERK1/2), suggesting that it may act via the mitogen‑activated protein kinase pathway. In summary, the present study identified fibulin‑5 as a downregulated ECM gene in human endometrial cancer and observed a shift from epithelial to stromal protein localisation with increasing tumour grade in women. These data suggest that loss of fibulin‑5 function may promote endometrial cancer progression by enhancing epithelial cell adhesion and proliferation.
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Copy and paste a formatted citation
Spandidos Publications style
Winship AL, Rainczuk K, Ton A and Dimitriadis E: Fibulin-5 localisation in human endometrial cancer shifts from epithelial to stromal with increasing tumour grade, and silencing promotes endometrial epithelial cancer cell proliferation. Oncol Lett 12: 651-657, 2016.
APA
Winship, A.L., Rainczuk, K., Ton, A., & Dimitriadis, E. (2016). Fibulin-5 localisation in human endometrial cancer shifts from epithelial to stromal with increasing tumour grade, and silencing promotes endometrial epithelial cancer cell proliferation. Oncology Letters, 12, 651-657. https://doi.org/10.3892/ol.2016.4650
MLA
Winship, A. L., Rainczuk, K., Ton, A., Dimitriadis, E."Fibulin-5 localisation in human endometrial cancer shifts from epithelial to stromal with increasing tumour grade, and silencing promotes endometrial epithelial cancer cell proliferation". Oncology Letters 12.1 (2016): 651-657.
Chicago
Winship, A. L., Rainczuk, K., Ton, A., Dimitriadis, E."Fibulin-5 localisation in human endometrial cancer shifts from epithelial to stromal with increasing tumour grade, and silencing promotes endometrial epithelial cancer cell proliferation". Oncology Letters 12, no. 1 (2016): 651-657. https://doi.org/10.3892/ol.2016.4650
Copy and paste a formatted citation
x
Spandidos Publications style
Winship AL, Rainczuk K, Ton A and Dimitriadis E: Fibulin-5 localisation in human endometrial cancer shifts from epithelial to stromal with increasing tumour grade, and silencing promotes endometrial epithelial cancer cell proliferation. Oncol Lett 12: 651-657, 2016.
APA
Winship, A.L., Rainczuk, K., Ton, A., & Dimitriadis, E. (2016). Fibulin-5 localisation in human endometrial cancer shifts from epithelial to stromal with increasing tumour grade, and silencing promotes endometrial epithelial cancer cell proliferation. Oncology Letters, 12, 651-657. https://doi.org/10.3892/ol.2016.4650
MLA
Winship, A. L., Rainczuk, K., Ton, A., Dimitriadis, E."Fibulin-5 localisation in human endometrial cancer shifts from epithelial to stromal with increasing tumour grade, and silencing promotes endometrial epithelial cancer cell proliferation". Oncology Letters 12.1 (2016): 651-657.
Chicago
Winship, A. L., Rainczuk, K., Ton, A., Dimitriadis, E."Fibulin-5 localisation in human endometrial cancer shifts from epithelial to stromal with increasing tumour grade, and silencing promotes endometrial epithelial cancer cell proliferation". Oncology Letters 12, no. 1 (2016): 651-657. https://doi.org/10.3892/ol.2016.4650
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