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Transforming growth factor-β regulates Kit ligand expression in rat ovarian surface epithelial cells

Oncogene volume 18, pages 4734–4741 (1999)Cite this article

Abstract

In preparation for ovulation, paracrine communication between the preovulatory follicle and overlying theca/stromal cells and ovarian surface epithelium (OSE) must take place to facilitate the degradative and apoptotic events associated with ovulation. Kit tyrosine kinase receptors and their ligand, kit ligand (KL) are expressed within ovarian follicles, and ligand-induced receptor activation appears to account for some of the cell – cell interactions important for oocyte development. We investigated the expression of Kit receptors and KL in OSE cells and the possibility that modulation of their expression could affect OSE cell activity. KL mRNA and protein were detected in the OSE cell layer of rat ovaries, and primary cultures of rat OSE as well as the immortalized rat OSE cell line, ROSE 199, expressed KL, but not Kit receptors. Both primary and immortalized OSE cells preferentially expressed KL-1, rather than KL-2, transcripts, suggesting that these cells produce predominantly the soluble form of KL. Activation of the cAMP signalling pathway using dibutyryl cAMP decreased proliferation of ROSE 199 cells and elicited a threefold increase in KL expression. TGF-β similarly inhibited ROSE 199 cell proliferation, but strongly inhibited dibutyryl cAMP-induced KL expression, indicating that changes in KL expression were not directly associated with OSE cell proliferation. The expression of mostly soluble KL in the surface epithelium suggests that this cytokine may be acting in a paracrine fashion, perhaps interacting with nearby Kit receptor-bearing theca cells.

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Acknowledgements

The authors wish to acknowledge technical assistance with the OSE PCR provided by Megan Hersh. We wish to thank Dr N Auersperg for the gift of ROSE 199 cells and Dr D Williams for the Sl4 cells. We are also grateful to AMGEN for providing the PCR primers and rat KL cDNAs, and to Dr A Bernstein for the mouse Kit cDNA. We would like to thank Sigma for their gift of penicillin-G. This research was supported by funds provided by the Cancer Research Society and the Medical Research Council of Canada.

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  1. Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa Regional Cancer Centre, 501 Smyth Road, Ottawa, K1H 8L6, Ontario, Canada

    Rubina S Ismail, Michaela Cada & Barbara C Vanderhyden

  2. Department of Medicine, University of Ottawa, Ottawa Regional Cancer Centre, 501 Smyth Road, Ottawa, K1H 8L6, Ontario, Canada

    Barbara C Vanderhyden

  3. Department of Obstetrics and Gynaecology, University of Ottawa, Ottawa Regional Cancer Centre, 501 Smyth Road, Ottawa, K1H 8L6, Ontario, Canada

    Barbara C Vanderhyden

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Ismail, R., Cada, M. & Vanderhyden, B. Transforming growth factor-β regulates Kit ligand expression in rat ovarian surface epithelial cells. Oncogene 18, 4734–4741 (1999). https://doi.org/10.1038/sj.onc.1202865

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