65 and 47 kDa forms of estrogen receptor in human breast cancer: relation with estrogen responsiveness

In breast cancer nearly 40% of estrogen receptor (ER) positive patients do not respond to hormone therapy. As several species of ER have been described, we examined 41 breast cancers for: (1) the presence of ER and progesterone receptor (PR); (2) the molecular weight (Mr) of ER; (3) estrogen responsiveness, appreciated by the ability of a piece of tumor transplanted in nude mice to show an estrogen-induced protein synthesis (PR synthesis). We found that there are: two species of ER with different Mr (65 and 47 kDa), and three species of tumors (36% containing the highest form of ER alone, 49% bearing the two components in variable amounts, and 15% bearing only the minor species). Eleven of these 41 tumors could be assayed for PR synthesis induction, showing that estrogen responsiveness is correlated with the major component. Due to the limited number of samples (11) the data are preliminary, but they strongly suggest that the different forms of ER could exist in the living cell with different functional abilities.