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Steroid-Modulated Proliferation of Human Endometrial Carcinoma Cell Lines: Any Role for Insulin-like Growth Factor Signaling?

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Abstract

Objectives

Estrogen-stimulated proliferation of the normal and malignant human endometrium is balanced by the differentiating properties of progesterone. This study evaluated the role of insulin-like growth factor (IGF) signaling in steroid-induced modulation of endometrial cancer cell proliferation.

Methods

We used the human endometrial, estrogen-responsive ECC-1 and progesterone-responsive PRAB-36 cell lines. Proliferation studies with IGFs in combination with either estrogen or progesterone were conducted. Furthermore, the mRNA and protein expression of insulin-like growth factor—binding proteins (IGFBPs) was evaluated.

Results

Using the ECC-1 cell line, we observed that estrogen-induced proliferation is modulated via the IGF-receptor signaling pathway, and that IGF- 1-induced stimulation of proliferation does not influence estrogen receptor signaling. Furthermore, expression of the main modulators of IGF action, the IGFBPs, was found to be regulated by estrogen and progesterone in both cell lines. IGFBP-4 was up-regulated by estrogen in the ECC-1 cell line, and IGFBP-3 and IGFBP-6 were down-regulated by progesterone in the PRAB-36 cell line.

Conclusion

Estrogen-induced stimulation of proliferation of ECC-1 endometrial cancer cells is partly achieved via IGF signaling. Furthermore, the IGFBPs are regulated by estrogens as well as progestagens and could potentially play a role in the modulation of endometrial cancer cell proliferation.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology and the Department of Reproduction and Development, Erasmus Medical Center, Rotterdam, The Netherlands

    Susanne C. J. P. Gielen MD, Eline E. Hanekamp MSc, Leen J. Blok PhD, Frans J. Huikeshoven MD, PhD & Curt W. Burger MD, PhD

  2. Department of Obstetrics and Gynecology, Ruwaard van Putten Hospital, Spijkenisse, The Netherlands

    Susanne C. J. P. Gielen MD, Eline E. Hanekamp MSc, Leen J. Blok PhD, Frans J. Huikeshoven MD, PhD & Curt W. Burger MD, PhD

Authors
  1. Susanne C. J. P. Gielen MD
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  2. Eline E. Hanekamp MSc
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  3. Leen J. Blok PhD
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Corresponding author

Correspondence to Susanne C. J. P. Gielen MD.

Additional information

Supported by a grant from the Erasmus Medical Center Rotterdam (EMC 820101).

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Gielen, S.C.J.P., Hanekamp, E.E., Blok, L.J. et al. Steroid-Modulated Proliferation of Human Endometrial Carcinoma Cell Lines: Any Role for Insulin-like Growth Factor Signaling?. Reprod. Sci. 12, 58–64 (2005). https://doi.org/10.1016/j.jsgi.2004.08.003

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  • DOI: https://doi.org/10.1016/j.jsgi.2004.08.003

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