PMID: 9449245Aug 1, 1997Paper

A novel estrogen receptor variant mRNA lacking exons 4 to 6 in breast carcinoma

The Journal of Steroid Biochemistry and Molecular Biology
C M Chan, M Dowsett

Abstract

A novel estrogen receptor mRNA splice variant which lacks the entire exon 5 and part of exon 4 and 6 was identified using reverse transcription PCR in human breast carcinomas. The variant was translated in vitro and produced a protein of approximately Mr 31000 which lacked the ligand binding domain. The binding of the variant estrogen receptor (ER) to a synthetic estrogen-responsive element (ERE) was compared with that of the wild-type ER (wtER). The variant ER bound weakly to the synthetic ERE, both in the presence and absence of estradiol, whilst the wtER bound strongly in the absence and the presence of estradiol. When wtER and variant ER were simultaneously translated in vitro, no heterodimerization was observed using band shift assay. Addition of increasing amounts of variant ER protein to the wtER in the ERE binding reaction showed that the variant protein competed with the binding of the wtER to the synthetic ERE. Furthermore, variant ER are not transcriptionally active. The variant was also expressed in 96% of the 102 breast tumours analysed, of which 62 were tamoxifen-resistant tumours. The expression of this variant was significantly higher (relative to ER) in untreated ER-positive breast tumours which were both proge...Continue Reading

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Citations

Sep 29, 2000·International Journal of Cancer. Journal International Du Cancer·S van der FlierM Dowsett
Dec 13, 2002·The Journal of Steroid Biochemistry and Molecular Biology·Tomoko ShodaKazuhiko Hoshi
Jan 20, 2000·Journal of the National Cancer Institute·S van der FlierJ A Foekens

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