Effects of cis- and trans-tamoxifen isomers on RNA incorporation of human breast cancer cells.

Cultured T47-D human breast cancer cells were used to investigate growth-inhibiting effects of the antiestrogen, trans-tamoxifen, on [3H]Cyd incorporation into specific classes of nuclear and cytoplasmic RNA. The steroid agonist, 17 beta-estradiol, and the inactive cis isomer of tamoxifen were used as treatment controls to compare antiestrogen-induced changes in RNA metabolism, independent of estrogen receptor-binding properties. Using a 24-hr labeling interval, trans-tamoxifen produced a 1.4- to 4-fold enhanced incorporation into pre-rRNA species (20S, 32-45S), with slight reduction in mature 18S rRNA incorporation, and a 2- to 3-fold increased incorporation into 5S and 5.8S rRNA and 4-4.5S tRNA. Most notable, trans-tamoxifen enhanced incorporation into the less abundant low molecular weight U1, U3, and 7S RNA species by 3- to 6-fold. These findings were associated with an apparent reduction in pre-rRNA content and little change in U1, U3, or 7S RNA levels in antiestrogen-treated cells, suggesting that trans-tamoxifen independently regulates RNA transcription and turnover. The present study provides new rationale for the choice of molecular probes to study trans-tamoxifen effects on synthesis and turnover of specific nuclear and cytoplasmic RNA species.