Open Access

Toll-like receptor 9 agonist inhibits ERα-mediated transactivation by activating NF-κB in breast cancer cell lines

  • Authors:
    • Jianming Qiu
    • Xiaojian Wang
    • Xinhai Guo
    • Chenyin Zhao
    • Xuhui Wu
    • Yongkui Zhang
  • View Affiliations

  • Published online on: October 1, 2009     https://doi.org/10.3892/or_00000520
  • Pages: 935-941
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Abstract

Primarily, Toll-like receptor 9 (TLR9) is a specific receptor for microbial DNA in human immune cells. TLR9 has been found to be a promising target in tumor immunotherapy but the direct effect of its activation on tumor cells remains unknown. In this study, we examined the effect of TLR9 ligation on estrogen receptor α (ERα)-mediated transactivation of breast cancer. Luciferase report gene assays, RNA interference of TLR9 and Chromatin immunoprecipitation were performed to measure the effect of TLR9 ligation on ERα-mediated transactivity of T47D and MCF-7 cells. Bromodeoxyuridine incorporation assay was used to examine the effect of TLR9 ligation on estrogen (E2)-induced proliferation of breast cancer cells. We also investigated the mechanism for the effect of TLR9 ligation on ERα-mediated transactivity. We found that ERα-mediated transcription via estrogen response element of human breast cancer cells line T47D was significantly suppressed when treated with 17β-estradiol in combination with TLR9 agonist CpG oligonucleotides and this effect of CpG was dependent on TLR9. Furthermore, nuclear factor κB (NF-κB) inhibitor BAY 11-7082 could abolish the inhibitory effect of CpG oligonucleotides on ERα-mediated transactivation. We also confirmed the effect of CpG oligonucleotides on ERα-mediated transactivation in the breast cancer cell line MCF-7 forced to stably overexpress TLR9. Finally, we observed that CpG oligonucleotides were also able to inhibit estrogen-induced proliferation of breast cancer cells as a consequence of decreased ERα-mediated transactivation. Taken together, our data suggest that TLR9 signal pathway, by activating NF-κB, negatively regulates ERα-mediated transactivation of breast cancer. Thus, TLR9 agonist inhibits the proliferation of breast cancer cells in response to estrogen.

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October 2009
Volume 22 Issue 4

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

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Spandidos Publications style
Qiu J, Wang X, Guo X, Zhao C, Wu X and Zhang Y: Toll-like receptor 9 agonist inhibits ERα-mediated transactivation by activating NF-κB in breast cancer cell lines. Oncol Rep 22: 935-941, 2009
APA
Qiu, J., Wang, X., Guo, X., Zhao, C., Wu, X., & Zhang, Y. (2009). Toll-like receptor 9 agonist inhibits ERα-mediated transactivation by activating NF-κB in breast cancer cell lines. Oncology Reports, 22, 935-941. https://doi.org/10.3892/or_00000520
MLA
Qiu, J., Wang, X., Guo, X., Zhao, C., Wu, X., Zhang, Y."Toll-like receptor 9 agonist inhibits ERα-mediated transactivation by activating NF-κB in breast cancer cell lines". Oncology Reports 22.4 (2009): 935-941.
Chicago
Qiu, J., Wang, X., Guo, X., Zhao, C., Wu, X., Zhang, Y."Toll-like receptor 9 agonist inhibits ERα-mediated transactivation by activating NF-κB in breast cancer cell lines". Oncology Reports 22, no. 4 (2009): 935-941. https://doi.org/10.3892/or_00000520