17 beta-estradiol dehydrogenase (E2DH) activity in T47D cells.
Activity of NAD-dependent 17 beta-hydroxysteroid dehydrogenase (E2DH), the enzyme which converts estradiol (E2) into its less active metabolite estrone (E1), has been previously characterized in normal human breast cells in culture and in benign and malignant breast tumors. E2DH activity is far greater in epithelial cells than in fibroblasts. Moreover, it is progesterone dependent in epithelial cells. It was therefore interesting to explore E2DH in the progesterone receptor (PR)-rich T47D cell line as a possible marker of hormone dependence in breast cancer cells. In T47D cells, transformation of [3H]E2 to E1 is limited. The metabolism seems to be preferentially oriented in the way E1----E2 in these cells. However, in the presence of the cofactor NAD the conversion of E2 into E1 increases. Moreover, treatment of T47D cells in culture by the progestin R5020 stimulates E2 to E1 conversion 2- to 3-fold. Stimulation of E2DH (E2----E1) activity reflects both the presence and the operability of PR. This observation underlines the possible interest of E2DH assay in parallel to estradiol receptor and PR to evaluate hormone-dependence of breast cancer.
Malet
C
C
Department of Endocrinology and Reproductive Medicine, Hôpital Necker, Paris, France.
Vacca
A
A
Kuttenn
F
F
Mauvais-Jarvis
P
P
D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D004960:Estradiol Dehydrogenases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D011397:Promegestone / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000032:analysis; D011987:Receptors, Steroid / Q000032:analysis
D011960:Receptors, Estrogen; D011987:Receptors, Steroid; D004958:Estradiol; D011397:Promegestone; D004960:Estradiol Dehydrogenases