Relative involvement of three 17β-hydroxysteroid dehydrogenases (types 1, 7 and 12) in the formation of estradiol in various breast cancer cell lines using selective inhibitors

We investigated the relative involvement of three reductive 17β-hydroxysteroid dehydrogenase (17β-HSD) isoforms, namely types 1, 7 and 12, in the formation of potent estrogen estradiol (E2) in 10 human breast cancer cell lines (T-47D, MCF-7, ZR-75-1, CAMA-1, BT-20, BRC-17, BRC-31, BRC-32, BRC-36 and BRN-196) and also in 1 choriocarcinoma cell line (JEG-3) using selective inhibitors. In T-47D, BT-20 and JEG-3 cells, a 17β-HSD1 inhibitor almost completely inhibited the formation of E2 at 1 μM from 60 nM of estrone (E1) (98%, 91% and 90%, respectively), whereas no significant inhibition of E2 formation was obtained using inhibitors of types 7 and 12. However, we obtained lower levels of inhibition (32%, 36% and 35% respectively using inhibitors of types 1, 7 and 12 at 10 μM) in MCF-7 cells and even lower and variable levels of inhibition (15%, 23% and 18% respectively using inhibitors of types 1, 7 and 12 at 10 μM) in ZR-75-1 cells. No inhibition of E2 formation was observed in CAMA-1 cells with a 17β-HSD1 inhibitor at 1 μM whereas inhibitors of types 7 and 12 inhibited 40% and 30% of E2 formation, respectively. In BRC and BRN cell lines, types 1, 7 and 12 17β-HSDs were all involved in the formation of E2, but type 12 seemed to predominate. At 10 μM, each inhibitor inhibited 10–50% of the formation of E2. Using MCF-7 and BRC-32 cell lines, a combination of the three inhibitors (3 × 10 μM) does not fully inhibit the 17β-HSD activity (65% and 75%). In addition to identify the relative importance of types 1, 7 and 12 17β-HSDs in the formation of E2 in human breast cancer cell lines, our results show also a great variability between each cell line. In some cases the formation of E2 was completely inhibited, but this was not the result observed in other cell lines, suggesting the presence of another enzyme involved in the biosynthesis of E2.