Hormone and cytotoxic drug responsiveness of cultured human breast cancer cells resistant to specific hormones.

Attempts have been made to develop sublines of MCF-7 cells resistant to the growth-inhibitory actions of medroxyprogesterone acetate (MPA), dexamethasone (DEX), anti-oestrogens or high-dose oestradiol (E2) by prolonged exposure to high hormone concentrations. While high degrees of resistance to MPA, DEX and E2 were achieved, cells remained anti-oestrogen-sensitive after prolonged treatment with 4 microM tamoxifen (TAM) or the anti-oestrogen LY 117018 (LY). Cells resistant to DEX were also resistant to MPA, while cells resistant to high-dose E2 remained sensitive to TAM.

Adriamycin action on human breast cancer cells: enhancement by medroxyprogesterone acetate.

Exposure of cultured human breast cancer cells (MCF-7) to medroxyprogesterone acetate (MPA) prior to treatment with adriamycin (ADR) enhanced the effect of the cytotoxic drug on cell yield after further growth of viable cells. Pretreatment with oestradiol (E2) produced similar synergism, but no such effect was observed using dexamethasone. Exposure to ADR before MPA led to an additive effect, but not to synergism.

Actions of medroxyprogesterone acetate on the efficacy of cytotoxic drugs: studies with human breast cancer cells in culture.

Human breast cancer cells (MCF-7) showed increased responses to methotrexate and vincristine after a 48-hr pre-treatment with medroxyprogesterone acetate. The effect of the hormone, which was detectable at concentrations of between 10 and 100 nM, was independent of its growth-inhibitory action. These findings confirm a previous clinical study and have important implications with regard to the management of advanced breast cancer.

The effects of sequential treatment with ethynyloestradiol and medroxyprogesterone acetate on oestrogen and progestogen receptors in breast cancer.

As part of a clinical study designed to modulate oestrogen and progestogen receptor (ER and PR) binding site concentrations prior to chemotherapy ER and PR levels have been estimated immediately before treatment, after ethynyloestradiol (EE, 10 micrograms/day, 1 week) and after medroxyprogesterone acetate (MPA, 500 mg/day i.m., 2 weeks) in tumour tissue from 14 women with advanced breast cancer.

Paracrine influence of human breast stromal fibroblasts on breast epithelial cells: secretion of a polypeptide which stimulates reductive 17 beta-oestradiol dehydrogenase activity.

We have previously shown that a stroma-associated paracrine influence may occur in the human breast. In particular, human breast fibroblasts secrete a factor which stimulates reductive 17 beta-oestradiol dehydrogenase (HSD) activity, thereby regulating tissue concentrations of 17 beta-oestradiol. We report here the results of experiments designed to establish the nature of the enzyme activity stimulating factor.