INSENSITIVITY OF CATHEPSIN-D GENE TO ESTRADIOL IN ENDOMETRIAL CELLS IS DETERMINED BY THE SEQUENCE OF ITS ESTROGEN-RESPONSIVE ELEMENT

In MCF7 cells, transcription of the lysosomal protease cathepsin D is stimulated by estrogens via a non-consensus estrogen responsive elemen t (ERE). By contrast, in estrogen responsive Ishikawa endometrial canc er cells, the cathepsin D gene is unresponsive to estrogens. We now sh ow that the transfected cathepsin D promoter, which can be induced by estrogens in several cell types, is insensitive in Ishikawa cells. The block is not due to a mutation in the cathepsin D promoter or estroge n receptor, but involves the cathepsin D ERE, and implies a C at posit ion 3 of the ERE sequence. Our results suggest that in Ishikawa cells, cathepsin D insensitivity to estrogen most likely occurs through a sp ecific interaction with the ER, or with an endometrial factor which ma y compete with the ER for binding to the cathepsin D ERE. (C) 1994 Aca demic Press, Inc.