AUTOREGULATION OF THE ESTROGEN-RECEPTOR PROMOTER

The presence or absence of estrogen receptor (ER) plays a key role in the diagnosis and treatment of breast tumors. It is known that patient s with breast tumors classified as ER-positive have a better prognosis . Observations such as this have led us to explore the question of wha t makes some breast tumors overexpress ER whereas others express eithe r very low levels or none at all. To begin a study of ER regulation, w e first chose to examine a 200 bp region of the ER promoter located im mediately upstream from the transcribed sequence of the human ER gene. We found that this region of the ER promoter contained basal activity when transiently transfected into ER-negative HeLa cells. ER promoter activity was further increased by co-transfection of a wild-type ER e xpression vector, and this increased activity was hormone-dependent, S everal ER deletion mutant constructs were also able to increase the ac tivity of the ER promoter fragment, but none could support equivalent activity as was seen with the full-length ER. Therefore, we conclude t hat the ER can contribute to its own expression, and we hypothesize th at this auto-regulation may contribute to its overexpression in some b reast tumors. (C) 1997 Elsevier Science Ltd.