Regulation of estrogen receptor α gene mediated by promoter B responsible for its enhanced expression in human breast cancer

Keiji Tanimoto, Hidetaka Eguchi, Takashi Yoshida, Kyoko Hajiro-Nakanishi, Shin Ichi Hayashi

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

We have previously reported that transcription from a distal promoter (promoter B) of the estrogen receptor or (ERα) gene is responsible for the increased expression of ERα 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 ERα mRNA transcribed from promoter B. Our findings indicate that ERBF-1 plays an important role in the expression of the ERα gene transcribed from promoter B, which is selectively utilized in breast cancer.

Original languageEnglish
Pages (from-to)903-909
Number of pages7
JournalNucleic acids research
Volume27
Issue number3
DOIs
Publication statusPublished - 1999 Feb 1
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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