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J Steroid Biochem. 1984 Jan;20(1):105-10.

Steroidal and nonsteroidal antiestrogens in breast cancer cells in culture.

Abstract

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.

PMID:
6368983
DOI:
10.1016/0022-4731(84)90196-1
[Indexed for MEDLINE]

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