ABSTRACT
We have examined the direct effects of progestins, oestrogens, peptide hormones and growth factors on oestradiol-17β 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, 6α-methyl-17α-hydroxyprogesterone acetate, norethisterone and d(−)-norgestrel all profoundly inhibited cell mitosis and stimulated reductive (oestrone→oestradiol-17β) and oxidative (oestradiol-17β→oestrone) OE2DH activity. Both oestrone and oestradiol-17β directly stimulated reductive OE2DH activity, but had no effect on the oxidative direction. Oestradiol-17β stimulated cell growth only in phenolred 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-17β levels observed in breast tissue during varying physiological and pathological conditions, such as during the menstrual cycle and in breast cancers.
J. Endocr. (1988) 118, 149–154
Transcriptional activation of collagenase-3 by transforming growth factor-β1 is via MAPK and Smad pathways in human breast cancer cells
