Recognition of the activated form of estrogen receptor bound to estradiol and tamoxifen by a monoclonal antibody
Giambiagi, N.; Pasqualini, J.R.
Pathologie-Biologie 34(8): 937-942
1986
ISSN/ISBN: 0369-8114 PMID: 3537937 Document Number: 280914
Two forms (alpha and beta) of the estrogen receptor were differentiated in the cytosol fraction of fetal guinea pig uterus by using a monoclonal antibody (D 547). Only the alpha form is recognised by the monoclonal antibody, shifting its sedimentation coefficient in high salt sucrose gradients, from 4.5 S to 7.5 S. Dynamic studies of the translocation of the receptor to the nucleus show a correlation between the decrease of the alpha form in the cytosol and the increase of the nuclear receptor concentration, suggesting that the alpha form translocates to the nucleus. Several factors such as time, temperature and high salt concentrations provoke a transformation of the beta form initially found in the cytosol, to the alpha form and induce the activation of the receptor, determined by an increase in its binding to DNA-cellulose. Sodium molybdate inhibits the transformation to the alpha form and the receptor activation. These data suggest that the alpha form, which is recognised by the antibody, is the activated form of the receptor. On the other hand, the estrogen receptor bound to tamoxifen can be activated by time, temperature and high salt concentrations and the activated form of the tamoxifen-receptor complex is also recognised by the monoclonal antibody D 547. However, the interaction with the monoclonal antibody and the binding to DNA-cellulose are less than those of the estradiol-receptor complex. These data support the hypothesis that the action of tamoxifen is related to its interaction with the estrogen receptor.