Maintenance of androgen responsiveness by glucocorticoids in Shionogi mammary carcinoma cells in culture.
The possibility that glucocorticoids can delay or prevent loss of responsiveness to androgens in androgen-deprived cells was investigated. While a complete loss of responsiveness to dihydrotestosterone (DHT) was observed within 60 days of androgen deprivation, addition of the synthetic glucocorticoid dexamethasone (DEX) delayed both the loss of growth responsiveness to DHT and the increase in spontaneous growth rate by approximately equal to 60 days. When the growth response to DEX was studied, the changes found were similar to those described above for DHT, namely loss of response following steroid deprivation and preservation of response in cells preincubated with DHT or DEX. In addition, long-term incubation in the presence of DEX was accompanied by low-amplitude stimulation of cell growth at extremely low concentrations of DHT and DEX, suggesting that androgen- and glucocorticoid-hypersensitive cell clones developed during androgen deprivation. The present data show that long-term incubation of androgen-sensitive Shionogi cells leads not only to an increase in the spontaneous growth rate, but also to the appearance of androgen- and glucocorticoid-hypersensitive cells, which may well play an important role in the development of resistance to endocrine therapy in human hormone-sensitive cancers. Although it is not as efficient as DHT, the glucocorticoid DEX can delay the loss of androgen sensitivity in this cell line.
Labrie
F
F
Medical Research Council (MRC) Group in Molecular Endocrinology, Laval University Medical Center, Quebec, Canada.
Veilleux
R
R
Fournier
A
A
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000728:Androgens; D005938:Glucocorticoids; D013196:Dihydrotestosterone; D003907:Dexamethasone