Estrogen formation in endometrial and cervix cancer cell lines: involvement of aromatase, steroid sulfatase and 17beta-hydroxysteroid dehydrogenases (types 1, 5, 7 and 12).
The involvement of aromatase, steroid sulfatase (STS) and reductive 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) in the production of estrogens was determined in four cell lines of endometrial cancer (Ishikawa, HEC-1A, HEC-1B and RL-95) and one cell line of cervix cancer (Hela) in culture. After incubation with 4-androstene-3,17-dione (4-dione), there are no estrogens, estrone (E1) and estradiol (E2), detected suggesting that the pathway of aromatase is not important in these cell lines. In whole cells, the results show low percentages of transformation of estrone sulfate (E1S) into E1 suggesting that the entrance of E1S is difficult. However, in homogenized cells the STS activity was much higher and fully blocked by an inhibitor. Using selective inhibitors for each reductive 17beta-HSD (types 1, 5, 7 and 12), alone or in combination, we did not succeed in completely blocking the conversion of E1 into E2, suggesting that another 17beta-HSD (known or unknown) is involved in the formation of E2 from E1.
Fournier
Michelle-Audrey
MA
Oncology and Molecular Endocrinology Laboratory, (Medicinal Chemistry Division), CHUQ-CHUL Research Center and Université Laval, Québec, Québec G1V 4G2, Canada.
Poirier
Donald
D
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D001141:Aromatase / Q000378:metabolism*; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000201:enzymology*; D004958:Estradiol / Q000737:chemistry / Q000378:metabolism; D004967:Estrogens / Q000096:biosynthesis*; D004970:Estrone / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D043266:Steryl-Sulfatase / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000201:enzymology*
D004967:Estrogens; D007527:Isoenzymes; D004970:Estrone; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D001141:Aromatase; D043266:Steryl-Sulfatase; C017296:estrone sulfate