Estrogen Receptor Expression and Function in Long-Term Estrogen-Deprived Human Breast Cancer Cells* * This work was supported by Grants NIH-RO-1-65622-04 (to R.J.S.), HD-25719 (to M.A.S.), GM-55985 and CA-44579 (to T.P.B.), and CA-65746 (to R.K.).

Hormone-dependent breast cancer responds to primary therapies that block estrogen production or action, but tumor regrowth often occurs 12–18 months later. Additional hormonal treatments that further reduce estrogen synthesis or more effectively block its action cause additional remissions, but the mechanisms responsible for these secondary responses are not well understood. As a working hypothesis, we postulated that primary hormonal therapy induces adaptive changes, resulting in enhanced estrogen receptor (ER) expression and target gene activation and, further, that secondary treatment modalities interfere with these receptor-mediated transcriptional pathways. To test this hypothesis, we used an MCF-7 breast cancer model system involving deprivation of estradiol in culture for a prolonged period. These long-term estradiol-deprived (LTED) cells adapt by acquiring the ability to regrow in the absence of added estradiol. The experimental paradigm involved the comparison of wild-type cells with LTED cells. ...

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