Estrogen target tissue determines alternative promoter utilization of the human estrogen receptor gene in osteoblasts and tumor cell lines.

Abstract

The estrogen receptor (ER) mediates the effects of its cognate ligand on important cellular processes such as development of female secondary sexual characteristics, establishment and maintenance of pregnancy, progression of breast cancer, and maintenance of bone mass. We have previously demonstrated that the human ER (hER) gene is transcribed from two promoters, suggesting that tissue- and cell-specific expression patterns of this gene may, at least in part, be regulated by differential promoter usage. Here we show, by using a reverse transcriptase coupled polymerase chain reaction assay, that transcripts initiated from both hER gene promoters were expressed in breast and uterus. In contrast, only transcripts originating from the distal promoter could be detected in human primary osteoblasts. Furthermore, determination of the expression levels of the two hER transcripts by quantitative polymerase chain reaction demonstrated an almost 30-fold increase of the transcripts originating from the proximal promoter in breast cancer cell lines over that detected in normal breast tissue. Taken together, our results demonstrate a previously unrecognized mechanism for regulation of hER gene expression by tissue-specific differential promoter utilization. In addition, our results suggest that estrogen-dependent cell transformation may be accompanied by a change in the relative expression levels of the two hER transcripts.