Biomedical subjects

S Bardon

Publications and source records attributed to S Bardon.

21 records · Page 2Linked to original sources

PubMed1984

Steroidal and nonsteroidal antiestrogens in breast cancer cells in culture.

The mode of action of two types of antiestrogens, tamoxifen and progestins, has been studied in the estrogen responsive cell lines, MCF7 and T47D, established from metastatic human breast cancer. (1) Non steroidal antiestrogens: We present evidence indicating that tamoxifen inhibits the growth of breast cancer cells via an interaction with the estrogen receptor (RE), which leads to a partial activation of the receptor and a dissociated effects on gene expression. At concentrations of less than 4 microM, effects of non steroidal antiestrogens are only observed when RE sites are available. At concentrations greater than 4 microM, an additional (cytotoxic?) effect of tamoxifen is observed which is not mediated by the RE. (2) Progestins: Direct antiestrogenic effect of progestins (R5020, progesterone) on breast cancer cells have been demonstrated. Three series of responses to R5020 are obtained: (a) A decreased cell proliferation (antiestrogenic and progestin specific effect). (b) A decreased production of total proteins in the culture medium (antiestrogenic effect). (c) The increased production of a 48,000 dalton protein which is released into the medium after treatment with several progestins (progesterone, medroxyprogesterone acetate, R5020) but not other steroids (specific progestin effect). These responses appear to be mediated by the progesterone receptor and are not observed in RP negative cell line (BT20). Even though these two types of antiestrogens inhibit cell proliferation via different receptors, a common final mechanism (decreased production of estrogen induced growth factors or increased production of antiestrogen induced inhibitory factor) is not excluded.

Breast Neoplasms↗

PubMed1984

The antiproliferative effect of tamoxifen in breast cancer cells: mediation by the estrogen receptor.

The effects of tamoxifen (Tam) and its 4-hydroxylated metabolite (OH-Tam) on the growth of two human breast cancer cell lines ( MCF7 and BT20 ) were evaluated by fluorometric DNA assay. The effects of the antiestrogens were dependent upon their concentrations and the nature of the cells. At concentrations below 4 microM, the degree of inhibition was related to their relative affinities for the estrogen receptor and was totally reversed by estradiol in MCF7 cells. No inhibition was observed in the estrogen receptor negative cell line BT20 . This supports and extends the idea that the antiproliferative effect of Tam at these concentrations is mediated by the estrogen receptor even in the absence of measurable estradiol concentration. At concentrations greater than 4 microM, Tam was cytotoxic on MCF7 and BT20 mammary cell lines within 2 days of treatment. The cytotoxic effect was irreversible and was not prevented by occupation of the estrogen receptor with estradiol, suggesting that it was not mediated by the estrogen receptor. The cytotoxicity of the triphenylethylene drugs, however, has some specificity since it was not observed in a fibroblast rat cell line ( 49F ) or in the two mammary cell lines with similar high concentrations of estradiol and diethylstilbestrol.

Breast Neoplasms↗

PubMed1983

Antiestrogenic effect of R5020, a synthetic progestin in human breast cancer cells in culture.

To see whether progestins prevent estrogen action in breast cancer cells, we have studied in vitro the effect of R5020 on the cell growth and the synthesis of secreted proteins in T47D and R27 human breast cancer cells. While R5020 had no effect on cell growth when tested alone, it significantly inhibited the growth of both cell lines in the presence of estradiol (1 nM). The effect was most clear-cut after 10-12 days of treatment and was dose dependent, a half-maximal inhibition occurred with 1 nM R5020. R27, a cloned MCF7 variant resistant to Tamoxifen, remained responsive to R5020, which prevented the effect of 17 beta-estradiol (E2) and inhibited cell growth in the presence of Tamoxifen. This suggests that the two antiestrogens are acting through different mechanisms. Dihydrotestosterone and dexamethasone did not reproduce or inhibit the effect of R5020 on cell growth. R5020 was ineffective in a rat tumor cell line containing androgen and glucocorticoid receptors but lacking progesterone receptors and estrogen receptors. These results suggest that R5020 is probably acting via progesterone receptors rather than via the androgen or glucocorticoid receptors. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we have shown that R5020 specifically decreases the production of the 52K protein, a major protein released by R27 cells after E2 stimulation. We conclude that R5020 has an antiestrogenic activity on breast cancer cells in culture, since it prevents the stimulation of cell growth and protein synthesis by E2.

Breast Neoplasms↗