An isotopic infusion technique has been used in an attempt to determine the contribution that local, in situ, oestrone synthesis makes to the oestrogen content of breast tumours. 3H-Androstenedione and 14C-oestrone were infused into women with advanced breast cancer for 12 hr before operation. At surgery, normal breast and breast tumour biopsy samples were obtained and 3H-androstenedione, 3H-oestrone derived from 3H-androstenedione and 14C-oestrone were isolated and measured. DNA polymerase alpha activity, a marker of cellular proliferation, was also measured to examine whether local synthesis of oestrone exerted a biological effect. The study was repeated after patients had been treated with the aromatase inhibitor, 4-hydroxyandrostenedione, before undergoing further surgery for removal of their tumours. In 4/6 tumours examined, in situ synthesis of 3H-oestrone from 3H-androstenedione accounted for the major part (84.3 +/- 9.0%) of the 3H-oestrone detected, while no significant in situ synthesis occurred in 2 other tumours. Although treatment with 4-hydroxyandrostenedione did not significantly alter the uptake of 3H-androstenedione or 14C-oestrone into breast tissues, in situ formation of 3H-oestrone was only detected in one tumour sample after treatment. DNA polymerase alpha activity decreased in 4/6 tumours after treatment with 4-hydroxyandrostenedione. Overall, however, there was no significant correlation between the level of 3H-oestrone formed in situ and DNA polymerase alpha activity (r = 0.38, NS). It is concluded that in some, but not all, breast tumours in situ formation of oestrone can make an important contribution to the oestrogen content of breast tumours.
The effect of conditioned medium from human breast fibroblasts on growth and 17 beta-estradiol dehydrogenase (E2DH) activity of the MCF-7 human breast cancer cell line has been investigated. Fibroblasts were derived from normal and tumorous (benign and malignant) breast tissue. Conditioned medium from normal derived fibroblasts inhibited the growth of MCF-7 cells, the effect being statistically significant by day 3 of culture. In contrast, conditioned medium from benign and malignant derived fibroblasts significantly enhanced the growth of MCF-7 cells by day 9 of culture. When added to MCF-7 cells for three days, conditioned medium from all three types of fibroblasts increased E2DH activity in the reductive direction (estrone (E1)----estradiol (E2] 2-3 fold. There was little or no effect on the oxidative direction (E2----E1). After 12 days, enzyme activity in the reductive direction was still markedly increased, the effect being greatest in conditioned medium from fibroblasts derived from malignant breast tissue, and least in conditioned medium from fibroblasts derived from benign breast tumors. These results demonstrate that human breast fibroblasts may have paracrine influences on neighboring epithelial cells in vivo.
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