Transformation of estrone and estradiol in hormone-dependent and hormone-independent human breast cancer cells. Effects of the antiestrogen ICI 164,384, danazol, and promegestone (R-5020).
Using different hormone-dependent (MCF-7, T-47D) and hormone-independent (MDA-MB-231, Hs-578S, MDA-MB-436) human breast cancer cells, the interconversion estrone (E1)<-->estradiol (E2) was explored. The data show very clearly that in the hormone-dependent cells the tendency is to form E2 after incubation with E1, whereas after incubation with E2 most of this estrogen remains unchanged. In the hormone-independent cells, in contrast most of E1 remains E1, while E2 is converted into E1. The tendency of the reductive<-->oxidative direction is supported by the analysis of estrogens in the culture medium. To explore the possible action of different drugs on the 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity, it was observed that the potent antiestrogen ICI 164,384 inhibits the conversion of E1 to E2, while a lesser effect is observed with Danazol and only weak inhibition is obtained with the progestagen Promegestone (R-5020). It is concluded that the orientation of 17 beta-HSD activity for the interconversion E1<-->E2 in hormone-dependent and -independent cells is related to the hormonal status of the cells.
Nguyen
B L
BL
C.N.R.S. Steroid Hormone Research Unit, Paris, France.
Chetrite
G
G
Pasqualini
J R
JR
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D001711:Biotransformation; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D003613:Danazol / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004970:Estrone / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism*; D053284:Polyunsaturated Alkamides; D011397:Promegestone / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D053284:Polyunsaturated Alkamides; D004970:Estrone; D004958:Estradiol; C051781:ICI 164384; D011397:Promegestone; D015067:17-Hydroxysteroid Dehydrogenases; D003613:Danazol