title: Role, control and expression of estrone sulfatase and 17 beta-hydroxysteroid dehydrogenase activities in human breast cancer.
abstract: Breast cancer tissue contains the enzymes necessary for local synthesis of estradiol (E2) and it was demonstrated that, despite the presence of the sulfatase and its messenger in hormone-dependent and hormone-independent breast cancer cells, this enzyme operates particularly in hormone-dependent cells. Different progestins: Nomegestrol acetate, Promegestone, Tibolone (Org OD14) and its metabolites (Org-OM38, Org 4098 and Org 30126), as well as Danazol, can block the conversion of estrone sulfate to E2 very strongly in hormone-dependent breast cancer cells. The last step in the formation of E2 is the conversion of estrone (E1) to estrogen by the action of 17 beta-hydroxysteroid dehydrogenase. This activity is preferentially in the reductive direction (formation of E2) in hormone-dependent cells, but oxidative (E2-->E1) in hormone-independent cells. Using intact hormone-dependent cells, it was observed that Nomegestrol acetate. Promegestone as well as Danazol, can block the conversion of E1 to E2. Clinical trials of these "anti-enzyme" substances in breast cancer patients could be the next step to investigate new therapeutic possibilities for this disease.
authors.affiliation: Steroid Hormone Research Unit, Paris, France.
authors.forename: J R
authors.initials: JR
authors.lastname: Pasqualini
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000502:physiology*; D001943:Breast Neoplasms / Q000201:enzymology*; D004958:Estradiol / Q000378:metabolism; D004970:Estrone / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology; D011374:Progesterone / Q000502:physiology; D045167:Progesterone Congeners / Q000494:pharmacology; D013429:Sulfatases / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
chemical_list: D045167:Progesterone Congeners; D004970:Estrone; D011374:Progesterone; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases; D013429:Sulfatases; C020121:estrone sulfatase; C017296:estrone sulfate