Le Bail J C, Marre-Fournier F, Nicolas J C, Habrioux G
UPRES EA 1085, Biomolécules et cibles cellulaires tumorales-Prolifération cellulaire et inhibition enzymatique, Faculté de Pharmacie, Limoges, France.
Steroids. 1998 Dec;63(12):678-83. doi: 10.1016/s0039-128x(98)00078-6.
The estrogenic action of C19 steroids on breast cancer cells was measured by bioluminescence in stably transfected human breast cancer MCF-7 and T47D cell lines with a reporter gene that allows expression of the firefly luciferase enzyme under control of an estrogen regulatory element. The "estrogenic activity" of C19 steroids, such as dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), androst-5-en-3 beta,17 beta-diol, androst-4-en-3,17-dione, dihydrotestosterone, testosterone, and 5 alpha-androstan-3 beta,17 beta-diol was studied. This showed that DHEAS, at concentration observed in physiological conditions (10(-6) M), had a high "estrogen-like effect" in MCF-7 and T47D cell lines. Other C19 steroids, at physiological plasma concentration, alone or together did not have any significant effect on the luciferase activity. Moreover aminoglutethimide, an inhibitor of the aromatase enzyme, in the presence of C19 steroids, partially decreased the luciferase activity. These results suggest that MCF-7 and T47D cell lines could convert DHEAS to estrogen-like compounds by different enzymatic systems.
通过生物发光法，在稳定转染了一种报告基因的人乳腺癌MCF - 7和T47D细胞系中测定C19类固醇对乳腺癌细胞的雌激素作用，该报告基因可使萤火虫荧光素酶在雌激素调节元件的控制下表达。研究了C19类固醇的“雌激素活性”，如脱氢表雄酮（DHEA）及其硫酸盐（DHEAS）、雄甾-5-烯-3β,17β-二醇、雄甾-4-烯-3,17-二酮、二氢睾酮、睾酮和5α-雄甾烷-3β,17β-二醇。结果表明，在生理条件下观察到的浓度（10^(-6) M）下，DHEAS在MCF - 7和T47D细胞系中具有较高的“雌激素样效应”。其他C19类固醇在生理血浆浓度下，单独或共同作用对荧光素酶活性均无显著影响。此外，芳香化酶抑制剂氨鲁米特在C19类固醇存在的情况下，可部分降低荧光素酶活性。这些结果表明，MCF - 7和T47D细胞系可能通过不同的酶系统将DHEAS转化为雌激素样化合物。
