Identification of an enhancer element in the estrogen receptor upstream region: implications for regulation of ER transcription in breast cancer.
The estrogen receptor (ER) serves as a diagnostic marker for the treatment of breast cancer. Patients with ER-positive breast tumors are likely to respond to hormonal therapies, while ER-negative breast cancers are resistant to endocrine therapies. Most ER-negative tumors do not express detectable levels of ER transcript, highlighting the importance of transcriptional regulation. A novel regulatory element which resembles a steroid hormone response element has been identified in the 5'-flanking region of the human ER gene. We observed 3- to 5-fold higher specific binding to this element in nuclear extracts from ER-expressing MCF-7 breast cancer cells compared to ER-negative MDA-MB-231 breast tumor cells. We termed the factor(s) which bind to this cis-element estrogen receptor upstream binding factor-1 (ERUBF-1). In transient transfection assays in MCF-7 cells, the ERUBF-1 binding site elicited a 20-fold increase in luciferase activity over the ER P1, promoter. This enhancer element was significantly more active in the ER-positive MCF-7 cell line compared to the ER-negative MDA-MB-231 cell line. These data indicate that ERUBF-1 plays an important role in the transcriptional regulation of the ER gene in breast cancer.
Cohn
C S
CS
Tulane Cancer Center, Department of Anatomy, Research Service, VAMC, New Orleans, LA 70146, USA.
Sullivan
J A
JA
Kiefer
T
T
Hill
S M
SM
D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms; D018983:DNA Footprinting; D004273:DNA, Neoplasm / Q000032:analysis; D004742:Enhancer Elements, Genetic; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009376:Neoplasms, Hormone-Dependent; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D011960:Receptors, Estrogen; D008156:Luciferases