Nuclear estrogen receptor-mediated Notch signaling and GPR30-mediated PI3K/AKT signaling in the regulation of endometrial cancer cell proliferation

  • Authors:
    • Yanan Wei
    • Zhenbo Zhang
    • Hong Liao
    • Ling Wu
    • Xiaomei Wu
    • Dongmei Zhou
    • Xiaowei Xi
    • Yaping Zhu
    • Youji Feng
  • View Affiliations

  • Published online on: November 8, 2011     https://doi.org/10.3892/or.2011.1536
  • Pages: 504-510
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Abstract

To elucidate the mechanisms of nuclear estrogen receptor (ER)-mediated and G protein-coupled receptor 30 (GPR30)-mediated signaling in the regulation of proliferation in ER-positive and ER-negative endometrial cancer cells, two human endometrial carcinoma cell lines, Ishikawa (ER-positive) and KLE (ER-negative), were used. PCR and Western blot analyses were used to determine the effects of estrogen stimulation on the activation of Notch and GPR30-PI3K/AKT signaling. Cell growth was investigated using MTT assays. Overexpression of ER in ER-negative cells was achieved by plasmid transfection and was used to investigate the effects on cellular growth and Notch signaling. GPR30-mediated signaling was evaluated using siRNA interference. Estrogen stimulated cell proliferation in both cell lines, it activated Notch signaling in ER-positive Ishikawa cells, but not in ER-negative KLE cells. Blockade of this signaling by a Notch inhibitor resulted in partial arrest of estrogen-induced cell proliferation in Ishikawa cells. Overexpression of ER in KLE cells restored estrogen-enhanced Notch signaling and further promoted cell growth. GPR30, as a new G-protein-coupled estrogen receptor, was detected in both cell lines, but was stronger in ER-negative KLE cells. Depletion of GPR30 in KLE cells abolished estrogen-induced PI3K/AKT signaling activation and resulted in inhibition of cell proliferation. Conclusively, regulation of proliferation in nuclear ER-positive endometrial cancer cells is mediated by both ER-Notch signaling and GPR30-PI3K/AKT signaling, whereas only the latter pathway is involved in the regulation of growth in nuclear ER-negative endometrial cancer cells.

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February 2012
Volume 27 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Wei Y, Zhang Z, Liao H, Wu L, Wu X, Zhou D, Xi X, Zhu Y and Feng Y: Nuclear estrogen receptor-mediated Notch signaling and GPR30-mediated PI3K/AKT signaling in the regulation of endometrial cancer cell proliferation. Oncol Rep 27: 504-510, 2012
APA
Wei, Y., Zhang, Z., Liao, H., Wu, L., Wu, X., Zhou, D. ... Feng, Y. (2012). Nuclear estrogen receptor-mediated Notch signaling and GPR30-mediated PI3K/AKT signaling in the regulation of endometrial cancer cell proliferation. Oncology Reports, 27, 504-510. https://doi.org/10.3892/or.2011.1536
MLA
Wei, Y., Zhang, Z., Liao, H., Wu, L., Wu, X., Zhou, D., Xi, X., Zhu, Y., Feng, Y."Nuclear estrogen receptor-mediated Notch signaling and GPR30-mediated PI3K/AKT signaling in the regulation of endometrial cancer cell proliferation". Oncology Reports 27.2 (2012): 504-510.
Chicago
Wei, Y., Zhang, Z., Liao, H., Wu, L., Wu, X., Zhou, D., Xi, X., Zhu, Y., Feng, Y."Nuclear estrogen receptor-mediated Notch signaling and GPR30-mediated PI3K/AKT signaling in the regulation of endometrial cancer cell proliferation". Oncology Reports 27, no. 2 (2012): 504-510. https://doi.org/10.3892/or.2011.1536