TY - JOUR
T1 - Regulation of estrogen receptor α gene mediated by promoter B responsible for its enhanced expression in human breast cancer
AU - Tanimoto, Keiji
AU - Eguchi, Hidetaka
AU - Yoshida, Takashi
AU - Hajiro-Nakanishi, Kyoko
AU - Hayashi, Shin Ichi
N1 - Funding Information:
We thank Dr Masakazu Toi (Tokyo Metropolitan Komagome Hospital) for providing cell lines and helpful discussion. We are grateful to Dr Etsuro Ogata (Cancer Institute Hospital, Tokyo) for his valuable suggestions and advice. This study was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan, for a 2nd-Term Comprehensive 10-Year Strategy for Cancer Control, from the Ministry of Health and Welfare of Japan.
PY - 1999/2/1
Y1 - 1999/2/1
N2 - 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.
AB - 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.
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U2 - 10.1093/nar/27.3.903
DO - 10.1093/nar/27.3.903
M3 - Article
C2 - 9889290
AN - SCOPUS:0033080781
VL - 27
SP - 903
EP - 909
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 3
ER -