ISSN:
1573-7217
Keywords:
androgens
;
antiestrogen
;
antiandrogen
;
androgen receptor
;
estrogen receptor
;
breast cancer
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary This study describes the inhibitory effect of 5α-dihydrotestosterone (5α-DHT) and its precursors testosterone (T) and androst-4-ene-3,17-dione (Δ4-DIONE) on the growth of the estrogen-sensitive human breast cancer cell line ZR-75-1. In the absence of estrogens, cell proliferation measured after a 12-day incubation period was 50–60% inhibited by maximal concentrations of 5α-DHT, T, or Δ4-DIONE with half-maximal effects (IC50 values) observed at 0.10, 0.15 and 15 nM, respectively. This growth inhibition by androgens was due to an increase in generation time and a lowering of the saturation density of cell cultures. The antiestrogen LY156758 (300 nM) induced 25–30% inhibition of basal cell growth, its effect being additive to that of 5α-DHT. The mitogenic effect of 1 nM estradiol (E2) was completely inhibited by increasing concentrations of 5α-DHT with a potency (IC50 = 0.10 nM) similar to that measured when the androgen was used alone. E2 had a more repid effect on cell proliferation than 5α-DHT, the latter requiring at least 5 to 6 days to exert significant growth inhibition. As found in the absence of estrogens, maximal inhibition of cell proliferation in the presence of E2 was achieved by the combination of the antiestrogen and 5α-DHT. Supraphysiological concentrations of E2 (up to 1µM) were needed to completely reverse the growth inhibitory effect of a submaximal concentration of 5α-DHT (1 nM). The antiproliferative effect of androgens was competitively reversed by the antiandrogen hydroxyflutamide, thus indicating an androgen receptor-mediated mechanism. The present data suggest the potential benefits of an androgen-antiestrogen combination therapy in the endocrine management of breast cancer.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01805942
