Immuno-biochemical assay for determination of nuclear steroid receptors during tamoxifen therapy

Abstract

The exact knowledge of hormone receptor status is critical for therapeutic strategies in hormone-dependent tumors. The influence of tamoxifen on estrogen receptor concentration has to be taken into account when evaluating results in tamoxifen-treated patients. We studied the receptor modulation of tumors xenotransplanted into nude mice (one breast and one endometrial carcinoma) after injection of 50 micrograms tamoxifen/mouse. To differentiate between unoccupied and occupied receptors, determinations were done by an enzyme immunoassay for the estrogen receptor under low- and high-salt extraction. With low-salt extraction we found a temporary decrease of the estrogen receptor concentration within the first hours after tamoxifen treatment. This decrease lasted for several days before recovery to pretreatment levels occurred. The hormone-receptor complexes, tightly bound to acceptor sites of the DNA, increased more than 15 times within 24 h. These values remained at increased levels for 2-7 days, after which a decrease to initial level was observed.

Hormonal prevention of breast cancer: proposal for a change in paradigm

“…It is important to note that, as progestogens decrease the production of their own receptors 87 , continuous administration might decrease breast cell responsiveness in time. However, addition of oestrogen, or an oestrogenic substance (such as tamoxifen) will maintain the production of the progesterone receptor 88,89 .…”

ICI 182,780 inhibits endogenous estrogen-dependent rat uterine growth and tamoxifen-induced developmental toxicity

“…Of considerable interest is our finding that tamoxifen demonstrates uterine cell-type specificity in its ability to increase ER immunoreactivity in the luminal epithelium and that this effect is inhibited by ICI 182,780. Tamoxifen-induced up-regulation of ER has been demonstrated in MCF-7 cells [42, 431, in endometrial tumors grown in nude mice [44,45], and in human breast cancer [461. However, other studies have shown that tamoxifen either decreased ER levels or did not alter ER levels in breast cancer tissue [47,48].…”