ESTROGEN-RECEPTOR ISOFORMS AND PROGESTIN HORMONE DEPENDENCE IN A MOUSE MAMMARY-TUMOR MODEL

The close interaction between receptors and other transcription factor s suggests that their corresponding transducing signals can trigger fu nctional and structural changes in other related molecules. The effect of a progestinic agent, medroxyprogesterone acetate (MPA), on some of the estrogen-receptor (ER) parameters was studied in 2 murine mammary tumor sublines with different progestine hormone dependence for their respective growth. The relative binding affinity of estradiol and tam oxifen for the ER, the receptor content and the ER isoforms studied by HPLC were determined in the hormone-autonomous (HA) and the hormone-d ependent (HD) tumor sublines. In the HA subline administration of MPA did not modify the tumor growth rate, whereas this was accelerated in the HD subline. The ER content was clearly increased in the HD tumor s ubline, but not in the HA subline, compared with the untreated control s. In contrast, the E(2) and tamoxifen relative binding affinity for t he ER and the isoform profiles were affected by MPA treatment in the H A, but not in the HD tumor subline. The functional change (decrease in relative binding affinity) can be attributed to the appearance of a l ower-molecular-size ER isoform under the progestinic treatment. Modifi cations in one receptor molecule by the action of ligands correspondin g to another type of receptor show the interconnection between transcr iption factors and the necessity of broadening conventional concepts r egarding hormone dependence in mammary tumorigenesis. (C) 1994 Wiley-L iss, Inc.