Regulation of estrogen receptor alpha gene mediated by promoter B responsible for its enhanced expressionin human breast cancer.
We have previously reported that transcription from a distal promoter (promoter B) of the estrogen receptor alpha (ERalpha) gene is responsible for the increased expression of ERalpha in human breast carcinomas. This paper first characterized the promoter B region in terms of transient transfection experiments with luciferase using MCF-7 cells. Gradual deletions from the 5'-end of promoter B resulted in a decrease in promoter activity corresponding to the deleted lengths; a deletion of 39 bp in a non-coding exon 1a, drastically diminished the activity, indicating existence of an important cis -element. Furthermore, electrophoretic mobility shift assay and subsequent mutational analysis indicated that this element containing nucleotide sequence CTGGAAAG forms a specific DNA-protein complex. This element was capable of transactivating a heterogeneous SV40 promoter in MCF-7 cells, confirming that the element is a transcriptional enhancer; the trans -acting factor binding to the element was named ERBF-1 (estrogen receptor promoter B associated factor-1). The ERBF-1 was exclusively expressed in those cells expressing ERalpha mRNA transcribed from promoter B. Our findings indicate that ERBF-1 plays an important role in the expression of the ERalpha gene transcribed from promoter B, which is selectively utilized in breast cancer.
Tanimoto
K
K
Hormone-Associated Cancer Research Group, Saitama Cancer Center Research Institute, Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806, Japan.
Eguchi
H
H
Yoshida
T
T
Hajiro-Nakanishi
K
K
Hayashi
S
S
D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004742:Enhancer Elements, Genetic; D047628:Estrogen Receptor alpha; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D018808:Transcription Factor AP-1; D014157:Transcription Factors