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Estrogen upregulates MICA/B expression in human non-small cell lung cancer through the regulation of ADAM17

Cellular & Molecular Immunology volume 12, pages 768–776 (2015)Cite this article

Abstract

Estrogen is involved in promoting lung cancer cell division and metastasis. MICA and MICB function as ligands for NKG2D, an important immunoreceptor expressed on natural killer (NK) cells. However, whether estrogen regulates MICA/B expression and affects tumor immune escape remains unknown. In this study, we measured the mRNA levels of MICA, MICB and ADAM17in non-small cell lung cancer (NSCLC) cell lines treated with estrogen. Surface expression of MICA/B on LTEP-a2 and A549 was detected using flow cytometry. We demonstrate that both mRNA and secretory protein levels of MICA/B in lung adenocarcinoma cell lines were upregulated by estradiol. Estradiol enhanced the expression of ADAM17, which was associated with the secretion of MICA/B. This secretion of MICA/B downregulated the NKG2D receptor on the surface of NK92 cells and impaired the cytotoxic activity of NK cells. Estradiol enhanced the expression of ADAM17, which was associated with the secretion of MICA/B. Furthermore, a significant correlation between the concentration of estradiol and the expression of MICA was found in tumor tissues of NSCLC patients. Therefore, we conclude that estrogen can regulate the expression and secretion of MICA/B through ADAM17, which helps lung cancer cells escape NKG2D-mediated immune surveillance.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81101552 and 81201598), and the Natural Science Foundation of Jiangsu Province (BK2011571).

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  1. Jing Ren and Yunzhong Nie: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Immunology, The State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, Nanjing, China

    Jing Ren, Yunzhong Nie, Mingming Lv, Sunan Shen, Ruijing Tang, Yujun Xu, Yayi Hou & Tingting Wang

  2. Jiangsu Key Laboratory of Molecular Medicine, Nanjing, China

    Sunan Shen, Yayi Hou & Tingting Wang

  3. State Key Laboratory of Reproductive Medicine, Central Laboratory of Nanjing First Hospital, Nanjing Medical University, Nanjing, China

    Shuli Zhao

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  1. Jing Ren
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Correspondence to Shuli Zhao or Tingting Wang.

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Supplementary Information accompanies the paper on Cellular & Molecular Immunology's website. (http://www.nature.com/cmi).

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Ren, J., Nie, Y., Lv, M. et al. Estrogen upregulates MICA/B expression in human non-small cell lung cancer through the regulation of ADAM17. Cell Mol Immunol 12, 768–776 (2015). https://doi.org/10.1038/cmi.2014.101

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