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 element (ERE). By contrast, in estrogen responsive Ishikawa endometrial cancer cells, the cathepsin D gene is unresponsive to estrogens. We now show 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 estrogen receptor, but involves the cathepsin D ERE, and implies a C at position 3 of the ERE sequence. Our results suggest that in Ishikawa cells, cathepsin D insensitivity to estrogen most likely occurs through a specific interaction with the ER, or with an endometrial factor which may compete with the ER for binding to the cathepsin D ERE.
Miralles
F
F
Unité Hormones et Cancer (U 148) INSERM, Montpellier, France.
Gaudelet
C
C
Cavailles
V
V
Rochefort
H
H
Augereau
P
P
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms; D056649:Cathepsin G; D002403:Cathepsins / Q000096:biosynthesis* / Q000235:genetics*; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic / Q000187:drug effects; D015183:Restriction Mapping; D012697:Serine Endopeptidases; D014162:Transfection; D014407:Tumor Cells, Cultured
D009838:Oligodeoxyribonucleotides; D004958:Estradiol; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; C534096:Ctsg protein, mouse