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Genomic and Nongenomic Effects of Estrogen Signaling in Human Endometrial Cells: Involvement of the Growth Factor Receptor Signaling Downstream AKT Pathway

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Abstract

For the endometrium, estradiol and tamoxifen induce proliferation, and consequently, tamoxifen treatment of breast cancer results in a 2-fold to 7-fold increased risk for endometrial cancer. Here, the role of activation of growth factor receptor signaling in mediating the e fects of estrogen and tamoxifen is determined. Microarray analysis of ECC-1 cells treated with estradiol or tamoxifen indicate that rapid responses to treatment (1 hour) are very distinct from long-term responses (> 24 hours). Furthermore, estradiol and tamoxifen are observed to induce AKT activation. Comparing long-term estrogen- and tamoxifen-regulated genes with genes regulated by insulin-like growth factor 1 and amphiregulin reveals that the late e fects of estrogen and tamoxifen signaling may partly be mediated via activation of growth factor receptor signaling pathways. It is hypothesized that both early and late e fects of estrogen and tamoxifen signaling in the endometrium are partly mediated via the activation of growth factor receptor signaling, putatively at the level of AKT activation.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Erasmus University Medical Center, Josephine Nefkens Institute, Room Ae 305, PO Box 1738, 3000 DR, Rotterdam, The Netherlands

    Sussane C. J. P. Gielen MD, PhD, Lindy A. M. Santegoets MD, Bianca Boers-Sijmons BSc, Payman Hanifi-Moghaddam PhD, Theo J. M. Helmerhorst MD, PhD, Leen J. Blok PhD & Curt W. Burger MD, PhD

  2. Department of Reproduction and Development, Eramus University Medical Center, Rotterdam, The Netherlands

    Liesbeth C. M. Kühne BSc

  3. Center for Biomics, Erasmus University Medical Center, Rotterdam, The Netherlands

    Wilfred F. J. Van IJcken PhD

  4. Department of Molecular Design and Informatics, Organon NV, Oss, The Netherlands

    Payman Hanifi-Moghaddam PhD

Authors
  1. Sussane C. J. P. Gielen MD, PhD
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  2. Lindy A. M. Santegoets MD
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  3. Liesbeth C. M. Kühne BSc
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  4. Wilfred F. J. Van IJcken PhD
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  5. Bianca Boers-Sijmons BSc
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  6. Payman Hanifi-Moghaddam PhD
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  7. Theo J. M. Helmerhorst MD, PhD
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  8. Leen J. Blok PhD
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  9. Curt W. Burger MD, PhD
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Corresponding author

Correspondence to Leen J. Blok PhD.

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Gielen, S.C.J.P., Santegoets, L.A.M., Kühne, L.C.M. et al. Genomic and Nongenomic Effects of Estrogen Signaling in Human Endometrial Cells: Involvement of the Growth Factor Receptor Signaling Downstream AKT Pathway. Reprod. Sci. 14, 646–654 (2007). https://doi.org/10.1177/1933719107306872

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  • DOI: https://doi.org/10.1177/1933719107306872

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