Abstract
Treatment of estrogen receptor (ER)-positive mammary tumors with tamoxifen produces a dramatic accumulation of ER in the cell nucleus. We investigated whether this phenomenon might be related to the antitumor activity of the drug. Five tamoxifen derivatives for which an influence on MCF-7 cell growth had previously been established were tested for that purpose; two of them inhibited growth, one was growth-stimulatory, and the remaining two were without significant effect. At 1 microM all compounds up-regulated ER in the cell nucleus after 3 days of culture, suggesting that the ER accumulation does not predict the response to tamoxifen treatment. An analysis of a tamoxifen-resistant clone (RT x 6 cells) under similar experimental conditions led to the same conclusion: the ER level significantly increased in the presence of tamoxifen and its 4-hydroxy metabolite.
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