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Induction of FGF receptor 2-IIIb expression and response to its ligands in epithelial ovarian cancer

Oncogene volume 20, pages 5878–5887 (2001)Cite this article

Abstract

Epithelial ovarian cancers (EOCs) arise in the Ovarian Surface Epithelium (OSE). This tissue is a simple, poorly committed mesothelium which exhibits characteristics of epithelial and mesenchymal cells when grown in culture. In contrast, EOCs frequently exhibit properties of complex epithelial tissues of the female reproductive tract, such as oviductal, endometrial and cervical epithelia, and show induction of expression of epithelial markers such as E-cadherin. Fibroblast Growth Factor Receptor 2 isoform IIIb (FGF receptor 2-IIIb) is a spliced variant of FGF receptor 2 that binds the ligands FGF-1 and FGF-7 with high affinity, and is expressed exclusively by epithelial cells. We have studied the expression of FGF receptor 2-IIIb and its ligands in primary cultures of normal human OSE, EOC cell lines and snap frozen tissue from EOCs. Expression of FGF receptor 2-IIIb mRNA is undetectable in normal OSE, but is expressed in 16/20 (80%) of EOCs. FGFs 1 and 7 mRNAs are expressed in normal OSE, whilst only 4/20 (20%) and 12/20 (60%) of EOCs demonstrated expression for these ligands respectively. However, FGF-7 protein was detected in 70% (mean level = 0.7 ng/ml) of ascitic fluids obtained from patients with EOC. FGFs 1 and 7 stimulate DNA synthesis in EOC cell lines that express FGF receptor 2-IIIb. Moreover, DNA synthesis in these cell lines can be partially blocked by blocking antisera to FGFs 1 and 7. It is suggested that induction of expression of FGF receptor 2-IIIb may play a role in the development of EOCs by rendering the OSE susceptible to paracrine and/or autocrine stimulation by its requisite FGF ligands.

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Acknowledgements

We would like to thank Dr Anne Wilson (Oncology Research Laboratory, Derby, UK) for providing some of the ovarian cancer ascitic fluid and Mrs Barbara Innes for technical assistance with the E-cadherin immunocytochemistry. This work was supported by a William Ross PhD studentship from the Cancer Research Campaign (CRC).

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Authors and Affiliations

  1. Department of Surgery, The Medical School, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, NE2 4HH, UK

    Islay A Steele, Hing Y Leung & Barry R Davies

  2. Northern Gynaecological Oncology Centre, Queen Elizabeth Hospital, Gateshead, UK

    Richard J Edmondson

  3. Department of Pathology, Royal Victoria Infirmary, Newcastle-upon-Tyne, NE2 4HH, UK

    Judith N Bulmer

  4. Department of Obstetrics and Gynaecology, Royal Victoria Infirmary, Newcastle-upon-Tyne, NE2 4HH, UK

    Brendan S Bolger

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  1. Islay A Steele
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Correspondence to Barry R Davies.

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Steele, I., Edmondson, R., Bulmer, J. et al. Induction of FGF receptor 2-IIIb expression and response to its ligands in epithelial ovarian cancer. Oncogene 20, 5878–5887 (2001). https://doi.org/10.1038/sj.onc.1204755

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