Estrogen receptor of primary breast cancers: evidence for intracellular proteolysis

Iodinated oestradiol-labeled oestrogen receptor (ER) isoforms devoid of ami no-terminal ABC domains represent about two-thirds of the whole receptor po pulation detected in cytosol samples from human breast cancers. This high f requency could not be ascribed to the expression of truncated mRNAs, or to the proteolysis of the native ER peptide at the time of homogenization or a ssay, suggesting an intracellular proteolysis. Free amino-terminal and liga nd-binding domains maintained together within oligomeric structure(s); incr ease of ionic strength separated them. The amino-terminal region was consis tently detected in the cell nucleus by specific immunohistochemistry leadin g to the concept of a potential intranuclear association between ER cleavag e products and/or other regulatory proteins.