Abstract
Oestrogens play an important role in the development of breast cancer. Oestrone sulphate (E 1 S) acts as a huge reservoir of oestrogens in the breast and is converted to oestrone (E 1 ) by oestrone sulphatase (E 1 STS). E 1 is then reversibly converted to the potent oestrogen, oestradiol (E 2 ) by oestradiol-17 hydroxysteroid dehydrogenase (E 2 DH). The aim of this study was to assess the effects of transforming growth factor- (TGF 1 ), insulin-like growth 1 factor-I (IGF-I) and insulin-like growth factor-II (IGF-II) on cell growth, E 1 STS and E 2 DH activities in the MCF-7 and MDAMB-231 human breast cancer cell lines. TGF 1, IGF-I and IGF-II alone or in combination inhibited cell growth of both cell lines but no additive or synergistic effects were observed. The treatments significantly stimulated E 1 STS activity in the MCF-7 cell line, except for TGF 1 alone and TGF 1 and IGFI in combination, where no effects were seen. Only TGF 1 and IGF-II acted synergistically to stimulate E 1 STS activity in the MCF-7 cells. There was no significant effect on E 1 STS activity in the MDA-MB-231 cells with any of the treatments. In the MCF-7 cells, TGF 1 and IGF-I, IGF-I and IGF-II, and TGF 1, IGF-I and IGF-II acted synergistically to stimulate the reductive E 2 DH activity, while only TGF 1, IGF-I and IGF-II synergistically stimulated the oxidative E 2 DH activity. There were no additive or synergistic effects on both oxidative and reductive E 2 DH activities in the MDA-MB-231 cells. In conclusion, TGF 1, IGF-I and IGF-II may have effects on oestrogen metabolism, especially in the MCF-7 cell line where they stimulated the conversion of E 1 S to E 1 and E 1 to E 2 and, thus, may have roles to play in the development of breast cancer.