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


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.
Funakoshi
Yasunobu
Y
Division of General Thoracic Surgery, Department of Surgery (E1), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871 Osaka, Japan.
Shiono
Hiroyuki
H
Inoue
Masayoshi
M
Kadota
Yoshihisa
Y
Ohta
Mitsunori
M
Matsuda
Hikaru
H
Okumura
Meinoshin
M
Eimoto
Tadaaki
T
D000328:Adult; D000368:Aged; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D005260:Female; D016193:G1 Phase / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D013945:Thymoma / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery*; D013953:Thymus Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery*
D005938:Glucocorticoids