Discussion:
Endogenous proteolysis is a regulatory mechanism in many cellular processes, such as cell cycle progression and transcriptional regulation. The present data extend this concept to ER. Indeed, proteolysis-generated ER fragments appear to be held together within the cell in oligomeric structures. Because ER proteolysis is probably relevant to several oestrogen target tissues, we suggest that the protein environment, which differs among tissues, may be a factor of major importance in the formation of distinct oligomeric structures, which elicit specific biological responses. The possibility of heterogeneous association between cleaved ER and regulatory proteins might perhaps result in a spectrum of such transcriptional activities. In this context, we propose that a complementary hydroxylapatite extraction assay (EI assessment) should be added to the usual tests to identify ER-positive tumours. Such a complementary test would provide an estimate of the level of cleaved ER forms, which may have biological and/or clinical relevance.