RESUMEN
Raloxifene (Ral) has estrogenic activity in bone and cardiovascular tissues, but is antiestrogenic in breast and has limited uterotrophic activity in mice. Here we report that Ral stimulates the growth of human endometrial Ishikawa tumors implanted in the mammary fat pad of nude ovariectomized mice. In cultured Ishikawa cells, Ral has agonist effects on transcription mediated by the progesterone receptor, an endogenous estrogen target gene, and on expression of reporter genes containing estrogen response elements (EREs). Both Ral and tamoxifen (Tam), but not estradiol, stimulated transcription mediated by the activator protein 1 at micromolar concentrations. However, this effect correlated with induction of cellular death at high concentrations of Ral or Tam and was not observed at lower concentrations. Our results suggest that Ral has stimulatory effects in Ishikawa cells on both cellular growth and gene transcription, and that EREs can mediate some of these effects.