Steroidal regulation of oestradiol-17 beta dehydrogenase activity of the human breast cancer cell line MCF-7.
We have examined the direct effects of progestins, oestrogens, peptide hormones and growth factors on oestradiol-17 beta dehydrogenase (OE2DH) activity of cultures of the human breast cancer cell line MCF-7. Cells were cultured in the presence of steroid or peptide for 6 days, after which the number of cells was determined and cellular OE2DH activity assessed. Progesterone, 6 alpha-methyl-17 alpha-hydroxyprogesterone acetate, norethisterone and D(-)-norgestrel all profoundly inhibited cell mitosis and stimulated reductive (oestrone----oestradiol-17 beta) and oxidative (oestradiol-17 beta----oestrone) OE2DH activity. Both oestrone and oestradiol-17 beta directly stimulated reductive OE2DH activity, but had no effect on the oxidative direction. Oestradiol-17 beta stimulated cell growth only in phenol-red free culture medium. Ovine prolactin, LH, epidermal growth factor and transforming growth factor did not alter OE2DH activity but small stimulatory effects on the growth of MCF-7 cells were exerted by prolactin and a combination of transforming growth factor with epidermal growth factor. It is concluded that these results may explain, at least in part, the alterations in mitotic activity and tissue oestradiol-17 beta levels observed in breast tissue during varying physiological and pathological conditions, such as during the menstrual cycle and in breast cancers.
Adams
E F
EF
Department of Chemical Pathology, St Mary's Hospital Medical School, London.
Coldham
N G
NG
James
V H
VH
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology*; D002460:Cell Line; D004960:Estradiol Dehydrogenases / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology; D013256:Steroids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000201:enzymology
D004967:Estrogens; D006133:Growth Substances; D010455:Peptides; D011372:Progestins; D013256:Steroids; D015067:17-Hydroxysteroid Dehydrogenases; D004960:Estradiol Dehydrogenases