Activation and immunorecognition by a monoclonal antibody of the tamoxifen-estrogen receptor complex.

The interaction of tamoxifen with the estrogen receptor of fetal guinea pig uterus, the activation of the tamoxifen-estrogen receptor complex and its immunorecognition by a monoclonal antibody raised against the human estrogen receptor is described in the present paper. The results show that: the tamoxifen-receptor complex sediments at 8 S in low-salt and at 4.5 S in high-salt sucrose gradients, this complex is partially recognized by the monoclonal antibody allowing the differentiation of two forms: the alpha form, which binds to the monoclonal antibody, and the beta form, which does not react with it; several factors such as time, temperature and high salt concentrations were capable of activating the tamoxifen-receptor complex, as determined by the increase of its binding to DNA-cellulose; these factors also induced a partial transformation of the beta form to the alpha form; sodium molybdate inhibited both activation and transformation of the beta into the alpha form. The correlation between activation and induction of the alpha form suggests that the monoclonal antibody recognizes selectively the activated form of the tamoxifen-receptor complex. These results indicate similar properties of the estrogen receptor when bound to either tamoxifen or estradiol; however, the differences observed in the behavior of the tamoxifen-receptor complex as compared with the estradiol-receptor complex, though quantitative rather than qualitative, suggest that the estrogen receptor is affected differently by tamoxifen and estradiol.