Evidence for two progesterone receptor binding sites in murine mammary carcinomas.
We have evaluated the progesterone receptor (PR) binding patterns in progestin-dependent and -independent murine mammary carcinomas; all variants regress completely after antiprogestin treatment. These studies revealed the presence of a high affinity, low capacity-binding site (K(d): 43 +/- 9 pM; Q=9 +/- 3 fmol/mg protein) and of the classical lower affinity, high capacity-binding site (K(d): 9.2 +/- 4.2 nM; Q=376 +/- 64 fmol/mg protein). These sites could also be detected in uterus. Antiprogestins were able to bind to both sites. In vitro, medroxyprogesterone acetate (MPA) was stimulatory along a biphasic curve with two slopes, one at very low concentrations (EC(50): 1.5 +/- 0.7 fM) and the other at values compatible with the described K(d) for the PR (EC(50): 0.33 +/- 0.3 nM).
Helguero
Luisa A
LA
Laboratory of Hormonal Carcinogenesis, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, C1428AND Buenos Aires, Argentina.
Lamb
Caroline
C
Molinolo
Alfredo A
AA
Lanari
Claudia
C
D000818:Animals; D001665:Binding Sites; D002277:Carcinoma / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D007700:Kinetics; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D045167:Progesterone Congeners / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology; D011485:Protein Binding; D011980:Receptors, Progesterone / Q000737:chemistry* / Q000378:metabolism*; D013997:Time Factors; D014599:Uterus / Q000378:metabolism
D045167:Progesterone Congeners; D011372:Progestins; D011980:Receptors, Progesterone; D017258:Medroxyprogesterone Acetate