Effect of transforming growth factor-β1, insulin-like growth factor-I and insulin-like growth factor-II on cell growth and oestrogen metabolism in human breast cancer cell lines

• Main Authors: Wong, Shew Fung, Reimann, Karin, Lai, Leslie C.
• Format: Article
• Language: English
• Published: Royal College of Pathologists of Australasia 2001
• Online Access: http://psasir.upm.edu.my/id/eprint/50002/1/Effect%20of%20transforming%20growth%20factor-%CE%B21%2C%20insulin-like%20growth%20factor-I%20and%20insulin-like%20growth%20factor-II%20on%20cell%20growth%20and%20oestrogen%20metabolism%20in%20human%20breast%20cancer%20cell%20lines.pdf; http://psasir.upm.edu.my/id/eprint/50002/; http://www.sciencedirect.com/science/article/pii/S0031302516345421

Oestrogens play an important role in the development of breast cancer. Oestrone sulphate (E1S) acts as a huge reservoir of oestrogens in the breast and is converted to oestrone (E1) by oestrone sulphatase (E1STS). E1 is then reversibly converted to the potent oestrogen, oestradiol (E2) by oestradiol-17β hydroxysteroid dehydrogenase (E2DH). The aim of this study was to assess the effects of transforming growth factor-β1 (TGFβ1), insulin-like growth factor-I (IGF-I) and insulin-like growth factor-II (IGF-II) on cell growth, E1STS and E2DH activities in the MCF-7 and MDA-MB-231 human breast cancer cell lines. TGFβ1, 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 E1STS activity in the MCF-7 cell line, except for TGF1 alone and TGF1 and IGF-I in combination, where no effects were seen. Only TGF1 and IGF-II acted synergistically to stimulate E1STS activity in the MCF-7 cells. There was no significant effect on E1STS activity in the MDA-MB-231 cells with any of the treatments. In the MCF-7 cells, TGFβ1 and IGF-I, IGF-I and IGF-II, and TGFβ1, IGF-I and IGF-II acted synergistically to stimulate the reductive E2DH activity, while only TGFβ1, IGF-I and IGF-II synergistically stimulated the oxidative E2DH activity. There were no additive or synergistic effects on both oxidative and reductive E2DH activities in the MDA-MB-231 cells. In conclusion, TGFβ1, IGF-I and IGF-II may have effects on oestrogen metabolism, especially in the MCF-7 cell line where they stimulated the conversion of E1S to E1 and E1 to E2 and, thus, may have roles to play in the development of breast cancer.