Identification of a novel estrogen response element in the Breast Cancer Resistance Protein (ABCG2) gene

The breast cancer resistance protein (BCRP) is an ATP-binding cassette half transporter that confers resistance to anticancer drugs such as mitoxantrone, anthracyclines, topotecan, and SN-38. Initial characterization of the BCRP promoter revealed that it is TATA-less with 5 putative Sp1 sites downst...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2004-02, Vol.64 (4), p.1247-1251
Main Authors: EE, Pui Lai, KAMALAKARAN, Sitharthan, TONETTI, Debra, XIAOLONG HE, ROSS, Douglas D, BECK, William T
Format: Article
Language:English
Subjects:
Antineoplastic agents
ATP Binding Cassette Transporter, Sub-Family G, Member 2
ATP-Binding Cassette Transporters - genetics
Biological and medical sciences
Estrogen Receptor alpha
Estrogens - pharmacology
Female
Humans
Medical sciences
Mutagenesis, Site-Directed
Neoplasm Proteins - genetics
Pharmacology. Drug treatments
Promoter Regions, Genetic
Receptors, Estrogen - metabolism
Response Elements
RNA, Messenger - analysis
Tumors
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Summary:The breast cancer resistance protein (BCRP) is an ATP-binding cassette half transporter that confers resistance to anticancer drugs such as mitoxantrone, anthracyclines, topotecan, and SN-38. Initial characterization of the BCRP promoter revealed that it is TATA-less with 5 putative Sp1 sites downstream from a putative CpG island and several AP1 sites (K. J. Bailey-Dell et al., Biochim. Biophys. Acta, 1520: 234-241, 2001). Here, we examined the sequence of the 5'-flanking region of the BCRP gene and found a putative estrogen response element (ERE). We showed that estrogen enhanced the expression of BCRP mRNA in the estrogen receptor (ER)-positive T47D:A18 cells and PA-1 cells stably expressing ERalpha. In BCRP promoter-luciferase assays, sequential deletions of the BCRP promoter showed that the region between -243 and -115 is essential for the ER effect. Mutation of the ERE found within this region attenuated the estrogen response, whereas deletion of the site completely abrogated the estrogen effect. Furthermore, electrophoretic mobility shift assays revealed specific binding of ERalpha to the BCRP promoter through the identified ERE. Taken together, we provide evidence herein for a novel ERE in the BCRP promoter.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-03-3583