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Glucocorticoids induce G1 cell cycle arrest in human neoplastic thymic epithelial cells

Journal of Cancer Research and Clinical Oncology volume 131, pages 314–322 (2005)Cite this article

Abstract

Purpose

Glucocorticoids exert anti-proliferative effects in various cell types and have long been known to induce apoptosis in thymocytes. Although a few reports have described the regression of human thymoma with glucocorticoid therapy, its effects on neoplastic thymic epithelial cells (TECs) have not been reported. In the present study, we investigated glucocorticoid receptor (GR) expression on neoplastic TECs and the effects of glucocorticoids in vitro on the cell cycle progression of tumor cells.

Patients and methods

Thymoma specimens were obtained during surgery from 21 patients. Three of the specimens with glucocorticoid therapy were examined using the TdT-mediated dUTP-biotin nick-end labeling method. Primary tumor specimens from ten untreated thymomas were examined for GR expression by immunohistochemistry. Isolated neoplastic TECs from the remaining eight untreated thymomas were examined using immunohistochemistry, flow cytometric and cell cycle analysis.

Results

GR are expressed on neoplastic TECs as well as on non-neoplastic thymocytes in thymomas, regardless of WHO histological classification. Glucocorticoids caused an accumulation of TEC in G0/G1 phase in all cases examined (n=6), and also induced apoptosis in the three with the lowest levels of Bcl-2 expression.

Conclusions

Our results indicate that neoplastic TECs express GR and that glucocorticoids directly suppress their in vitro proliferation.

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Abbreviations

GR:

Glucocorticoid receptor

TEC:

Thymic epithelial cell

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Acknowledgements

We are grateful to Nick Willcox for critically reading the manuscript. We wish to thank Keiji Iuchi (National Kinki Central Hospital), Katsuhiro Nakagawa (Osaka Prefectural Habikino Hospital), Hajime Maeda (National Toneyama Hospital), Hirohumi Sueki (Ohtemae Hospital), Hiroto Tada (Osaka City General Hospital), Hyung-Eng Yoon (Rinku Medical Center), Akinori Akashi, Yukiyasu Takeuchi (Takarazuka City Hospital), Tetsuo Kido (Osaka Police Hospital), and Yoshitomo Okumura (Hyogo Medical University) for their submission of the specimens, and also Al Averbach for editing the manuscripts

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Affiliations

  1. Division of General Thoracic Surgery, Department of Surgery (E1), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Osaka, Japan

    Yasunobu Funakoshi, Hiroyuki Shiono, Masayoshi Inoue, Yoshihisa Kadota, Mitsunori Ohta & Hikaru Matsuda

  2. Department of General Thoracic Surgery, National Kinki Central Hospital, Sakai, Osaka, Japan

    Meinoshin Okumura

  3. Department of Pathology, Nagoya City University Medical School, Nagoya, Japan

    Tadaaki Eimoto

Authors
  1. Yasunobu Funakoshi
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  2. Hiroyuki Shiono
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  3. Masayoshi Inoue
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  4. Yoshihisa Kadota
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  5. Mitsunori Ohta
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  6. Hikaru Matsuda
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  7. Meinoshin Okumura
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  8. Tadaaki Eimoto
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Correspondence to Hiroyuki Shiono.

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Funakoshi, Y., Shiono, H., Inoue, M. et al. Glucocorticoids induce G1 cell cycle arrest in human neoplastic thymic epithelial cells. J Cancer Res Clin Oncol 131, 314–322 (2005). https://doi.org/10.1007/s00432-004-0646-8

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  • DOI: https://doi.org/10.1007/s00432-004-0646-8

Keywords

  • Thymoma
  • Thymic epithelial cell
  • Glucocorticoid
  • Glucocorticoid receptor
  • Apoptosis